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Ghazwani M, Hani U, Kyada A, Ballal S, Issa BS, Abosaoda MK, Singh A, Sabarivani A, Ray S. Advancements in insulin delivery: the potential of natural polymers for improved diabetes management. Front Bioeng Biotechnol 2025; 13:1566743. [PMID: 40352348 PMCID: PMC12062796 DOI: 10.3389/fbioe.2025.1566743] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2025] [Accepted: 04/16/2025] [Indexed: 05/14/2025] Open
Abstract
Diabetes is a growing global health issue, with millions of people affected by the condition. While insulin therapy is vital for managing both Type 1 and Type 2 diabetes, traditional methods such as subcutaneous injections have notable drawbacks, including pain, discomfort, and difficulty in maintaining stable blood sugar levels. To improve insulin delivery, research is increasingly focused on the use of natural polymers-substances derived from plants, animals, and microorganisms. These polymers, including materials like alginate, chitosan, and hyaluronic acid, have promising properties such as biocompatibility, biodegradability, and the ability to provide controlled, sustained insulin release. By encapsulating insulin in polymers, it is protected from degradation and released in a manner that more closely mirrors the body's natural insulin production. Furthermore, the development of non-invasive delivery methods, such as oral and transdermal systems, is gaining momentum, offering the potential for more patient-friendly treatment options. This review discusses the role of natural polymers in insulin delivery, examining their mechanisms, types, and current research efforts. It also addresses the challenges that remain in advancing these technologies into practical clinical use, aiming to provide more efficient, comfortable, and effective solutions for diabetes management.
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Affiliation(s)
- Mohammed Ghazwani
- Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha, Saudi Arabia
| | - Umme Hani
- Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha, Saudi Arabia
| | - Ashishkumar Kyada
- Department of Pharmaceutical Sciences, Marwadi University Research Center, Faculty of Health Sciences, Marwadi University, Rajkot, Gujarat, India
| | - Suhas Ballal
- Department of Chemistry and Biochemistry, School of Sciences, JAIN (Deemed to be University), Bangalore, Karnataka, India
| | | | - Munthar Kadhim Abosaoda
- College of Pharmacy, The Islamic University, Najaf, Iraq
- College of pharmacy, The Islamic University of Al Diwaniyah, Al Diwaniyah, Iraq
| | - Abhayveer Singh
- Centre for Research Impact and Outcome, Chitkara University Institute of Engineering and Technology, Chitkara University, Rajpura, Punjab, India
| | - A. Sabarivani
- Department of Biomedical, Sathyabama Institute of Science and Technology, Chennai, Tamil Nadu, India
| | - Subhashree Ray
- Department of Biochemistry,IMS and SUM Hospital, Siksha ‘O’ Anusandhan (Deemed to be University), Bhubaneswar, Odisha, India
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Hussain Y, You BG, Huang L, Liu X, Dormocara A, Shah KA, Ali T, Cao QR, Lee BJ, Elbehairi SEI, Iqbal H, Cui JH. Dissolving microneedles for melanoma: Most recent updates, challenges, and future perspectives. Int J Pharm 2025; 673:125382. [PMID: 39988214 DOI: 10.1016/j.ijpharm.2025.125382] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2024] [Revised: 02/08/2025] [Accepted: 02/19/2025] [Indexed: 02/25/2025]
Abstract
Skin cancer is one among the common types of cancers, affecting millions of individual globally. The conventional anticancer therapy such as chemotherapy results in worst systemic and local side effects as well as inhibit the growth of healthy cells around the tumor cells. Dissolving microneedles (DMNs) is a groundbreaking technology with less invasive and more targeted features. Physically, these tiny dissolving needles deliver the anticancer payloads drug to the tumor site after its direct application on the skin surface. Specifically, the DMNs release the anticancer drug cargoes into the cancerous cell sparing the healthy cells around the tumor, thus has provided a significant contribution in the landscape of traditional skin cancer therapy. This targeted therapeutic approach of dissolving microneedles shows a significant therapeutic outcome in decreasing the growth of cancer cells in pre-clinical studies. Dissolving microneedles (DMNs) have demonstrated effectiveness in the targeted delivery of drugs, genes, and vaccines specifically at the site of skin tumors. This method mimics the localized release of adjuvants and immunomodulators, leading to significant humoral and cellular immune responses that are beneficial for skin cancer therapy. In this review, the current trends and potential roles of dissolving microneedles in delivering therapeutic agents focused on treating skin melanoma have been highlighted, drawing insights from recent literature. This emphasizes the promising applications of DMNs in enhancing treatment outcomes for skin cancer patients. Lastly, future perspectives were identified for improving the therapeutic potential and translation of DMNs into clinic.
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Affiliation(s)
- Yaseen Hussain
- College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China
| | - Ben-Gang You
- College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China
| | - Linyu Huang
- College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China
| | - Xiaoyin Liu
- School of Radiation Medicine and Protection of Soochow University, Suzhou 215123, China
| | - Amos Dormocara
- College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China
| | - Kiramat Ali Shah
- College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China
| | - Tariq Ali
- Department of Civil and Environmental Engineering, Shantou University, Shantou, Guangdong 515063, China
| | - Qing-Ri Cao
- College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China
| | - Beom-Jin Lee
- College of Pharmacy, Ajou University, Suwon 16499, Republic of Korea
| | | | - Haroon Iqbal
- State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China.
| | - Jing-Hao Cui
- College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
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El-Tanani M, Satyam SM, Rabbani SA, El-Tanani Y, Aljabali AAA, Al Faouri I, Rehman A. Revolutionizing Drug Delivery: The Impact of Advanced Materials Science and Technology on Precision Medicine. Pharmaceutics 2025; 17:375. [PMID: 40143038 PMCID: PMC11944361 DOI: 10.3390/pharmaceutics17030375] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2025] [Revised: 03/09/2025] [Accepted: 03/12/2025] [Indexed: 03/28/2025] Open
Abstract
Recent progress in material science has led to the development of new drug delivery systems that go beyond the conventional approaches and offer greater accuracy and convenience in the application of therapeutic agents. This review discusses the evolutionary role of nanocarriers, hydrogels, and bioresponsive polymers that offer enhanced drug release, target accuracy, and bioavailability. Oncology, chronic disease management, and vaccine delivery are some of the applications explored in this paper to show how these materials improve the therapeutic results, counteract multidrug resistance, and allow for sustained and localized treatments. The review also discusses the translational barriers of bringing advanced materials into the clinical setting, which include issues of biocompatibility, scalability, and regulatory approval. Methods to overcome these challenges include surface modifications to reduce immunogenicity, scalable production methods such as microfluidics, and the harmonization of regulatory systems. In addition, the convergence of artificial intelligence (AI) and machine learning (ML) is opening new frontiers in material science and personalized medicine. These technologies allow for predictive modeling and real-time adjustments to optimize drug delivery to the needs of individual patients. The use of advanced materials can also be applied to rare and underserved diseases; thus, new strategies in gene therapy, orphan drugs development, and global vaccine distribution may offer new hopes for millions of patients.
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Affiliation(s)
- Mohamed El-Tanani
- RAK College of Pharmacy, Ras Al Khaimah Medical and Health Sciences University, Ras Al Khaimah P.O. Box 11172, United Arab Emirates
| | - Shakta Mani Satyam
- Department of Pharmacology, RAK College of Medical Sciences, Ras Al Khaimah Medical and Health Sciences University, Ras Al Khaimah P.O. Box 11172, United Arab Emirates
| | - Syed Arman Rabbani
- RAK College of Pharmacy, Ras Al Khaimah Medical and Health Sciences University, Ras Al Khaimah P.O. Box 11172, United Arab Emirates
| | | | - Alaa A. A. Aljabali
- Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Yarmouk University, Irbid 21163, Jordan;
| | - Ibrahim Al Faouri
- RAK College of Nursing, Ras Al Khaimah Medical and Health Sciences University, Ras Al Khaimah P.O. Box 11172, United Arab Emirates
| | - Abdul Rehman
- Department of Pathology, RAK College of Medical Sciences, Ras Al Khaimah Medical and Health Sciences University, Ras Al Khaimah P.O. Box 11172, United Arab Emirates;
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Li L, Wang Y. Advancements in Injectable Hydrogels for Controlled Insulin Delivery: A Comprehensive Review of the Design, Properties and Therapeutic Applications for Diabetes and Its Complications. Polymers (Basel) 2025; 17:780. [PMID: 40292663 PMCID: PMC11944538 DOI: 10.3390/polym17060780] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2025] [Revised: 03/09/2025] [Accepted: 03/12/2025] [Indexed: 04/30/2025] Open
Abstract
Glycemic management in diabetes patients remains heavily reliant on multiple daily insulin injections, which often leads to poor patient compliance and an elevated risk of hypoglycemia. To overcome these limitations, injectable hydrogels capable of encapsulating insulin within polymeric networks have emerged as a promising alternative. Ideally, a single injection can form an in situ depot that allows prolonged glycemic control and lower injection frequency. This review summarizes recent advances in injectable hydrogels for controlled insulin delivery, focusing on the polymer sources, crosslinking strategies, and stimuli-responsive release mechanisms. Synthetic polymers such as PEG, PNIPAM, and Pluronics dominate the current research due to their highly tunable properties, whereas naturally derived polysaccharides and proteins generally require further modifications for enhanced functionality. The crosslinking types, ranging from relatively weak physical interactions (hydrogen bonds, hydrophobic interactions, etc.) to dynamic covalent bonds with higher binding strength (e.g., Schiff base, phenylboronate ester), significantly influence the shear-thinning behavior and stimuli-responsiveness of hydrogel systems. Hydrogels' responsiveness to temperature, glucose, pH, and reactive oxygen species has enabled more precise insulin release, offering new options for improved diabetic management. Beyond glycemic regulation, this review also explores insulin-loaded hydrogels for treating complications. Despite the progress, challenges such as burst release, long-term biocompatibility, and scalability remain. Future research should focus on optimizing hydrogel design, supported by robust and comprehensive data.
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Affiliation(s)
| | - Ya Wang
- Guangdong Provincial/Zhuhai Key Laboratory of IRADS, and Department of Life Sciences, BNU-HKBU United International College, Zhuhai 519087, China;
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Asaad GF, Doghish AS, Rashad AA, El-Dakroury WA. Exploring cutting-edge approaches in diabetes care: from nanotechnology to personalized therapeutics. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025; 398:2443-2458. [PMID: 39453501 PMCID: PMC11919990 DOI: 10.1007/s00210-024-03532-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Accepted: 10/08/2024] [Indexed: 10/26/2024]
Abstract
Diabetes mellitus (DM) is a persistent condition characterized by high levels of glucose in the blood due to irregularities in the secretion of insulin, its action, or both. The disease was believed to be incurable until insulin was extracted, refined, and produced for sale. In DM, insulin delivery devices and insulin analogs have improved glycemic management even further. Sulfonylureas, biguanides, alpha-glucosidase inhibitors, and thiazolidinediones are examples of newer-generation medications having high efficacy in decreasing hyperglycemia as a result of scientific and technological advancements. Incretin mimetics, dual glucose-dependent insulinotropic polypeptide, GLP-1 agonists, PPARs, dipeptidyl peptidase-4 inhibitors, anti-CD3 mAbs, glucokinase activators, and glimins as targets have all performed well in recent clinical studies. Considerable focus was placed on free FA receptor 1 agonist, protein tyrosine phosphatase-1B inhibitors, and Sparc-related modular calcium-binding protein 1 which are still being studied. Theranostics, stem cell therapy, gene therapy, siRNA, and nanotechnology are some of the new therapeutic techniques. Traditional Chinese medicinal plants will also be discussed. This study seeks to present a comprehensive analysis of the latest research advancements, the emerging trends in medication therapy, and the utilization of delivery systems in treating DM. The objective is to provide valuable insights into the application of different pharmaceuticals in the field of diabetes mellitus treatment. Also, the therapeutic approach for diabetic patients infected with COVID-19 will be highlighted. Recent clinical and experimental studies evidence the Egyptian experience. Finally, as per the knowledge of the state of the art, our conclusion and future perspective will be declared.
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Affiliation(s)
- Gihan F Asaad
- Department of Pharmacology, Medical Research and Clinical Studies Institute, National Research Centre, Giza, Egypt
| | - Ahmed S Doghish
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt
- Department of Biochemistry and Molecular Biology, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Cairo, 11651, Egypt
| | - Ahmed A Rashad
- Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt
| | - Walaa A El-Dakroury
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt.
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Cai Y, Zhang L, Cheng W, Xu W, Yuan K, Xiong R, Huang C. On-demand release of insulin using glucose-responsive chitosan-based three-compartment microspheres. Int J Biol Macromol 2025; 293:139351. [PMID: 39743064 DOI: 10.1016/j.ijbiomac.2024.139351] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Revised: 12/13/2024] [Accepted: 12/28/2024] [Indexed: 01/04/2025]
Abstract
Various injectable glucose-responsive insulin release systems, including microspheres, have been developed to achieve insulin release for over a day. However, a major challenge is on-demand release insulin, which is closely related to the degradation rate of the delivery vehicle. Herein, chitosan-based three-compartment microspheres (TCMs) were fabricated using gas-shearing microfluidics. Glucose reacts with glucose oxidase (GOD) to generate gluconic acid, and chitosan degrades under acidic conditions to release insulin. The chitosan concentration in each compartment is adjusted to have gradient pH response ranges. Low, medium and high concentrations of insulin are encapsulated in low, medium and high concentration chitosan compartments respectively. The number of compartments involved in insulin release increases from one to three as blood glucose rises. Compared with single one-compartment microspheres (OCMs), TCMs maintain structural integrity and drug action for a longer duration. In vitro experiments have proven the on-demand release of insulin and excellent biocompatibility of TCMs. In chemically induced type 2 diabetes cell models, TCMs demonstrated long-term regulation of blood glucose levels for 20 to 35 h. This work presents a novel concept of constructing three compartments in microspheres to release insulin on-demand, and is highly attractive for research on insulin analogs and other related application.
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Affiliation(s)
- Yixin Cai
- Joint Laboratory of Advanced Biomedical Materials (NFU-UGent), Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, College of Chemical Engineering, Nanjing Forestry University, Nanjing 210037, China
| | - Louqian Zhang
- Department of Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210000, PR China
| | - Weixia Cheng
- Children's Hospital of Nanjing Medical University, Nanjing 210008, PR China
| | - Wenxuan Xu
- Joint Laboratory of Advanced Biomedical Materials (NFU-UGent), Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, College of Chemical Engineering, Nanjing Forestry University, Nanjing 210037, China
| | - Kangrui Yuan
- Joint Laboratory of Advanced Biomedical Materials (NFU-UGent), Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, College of Chemical Engineering, Nanjing Forestry University, Nanjing 210037, China
| | - Ranhua Xiong
- Joint Laboratory of Advanced Biomedical Materials (NFU-UGent), Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, College of Chemical Engineering, Nanjing Forestry University, Nanjing 210037, China.
| | - Chaobo Huang
- Joint Laboratory of Advanced Biomedical Materials (NFU-UGent), Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, College of Chemical Engineering, Nanjing Forestry University, Nanjing 210037, China.
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Kłapcia A, Domalik-Pyzik P. Hydrogel Dressings as Insulin Delivery Systems for Diabetic Wounds. Front Biosci (Elite Ed) 2025; 17:26446. [PMID: 40150982 DOI: 10.31083/fbe26446] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Revised: 10/29/2024] [Accepted: 11/08/2024] [Indexed: 03/29/2025]
Abstract
Diabetic wounds are one of the most common and challenging complications of diabetes. Similar to chronic wounds, diabetic wounds are difficult to treat due to prolonged inflammation, a lack of angiogenesis, abnormal differentiation of new scar tissue, and the occurrence of numerous bacterial infections. Moreover, elevated sugar levels in tissues disrupt the healing process by enhancing inflammatory reactions, disrupting signaling pathways, and leading to the production of abnormal biological structures, which contribute to improper cell differentiation. Traditional dressings, such as bandages, gauze, and semi-occlusive foams, are inadequate for diabetic wounds with high exudation; moreover, frequently changing the dressing can cause secondary irritation. Hence, innovative hydrogel dressings are being developed, which, thanks to their soft polymer matrix, provide an ideal substrate for regenerating tissue. Hydrogels also allow for the introduction and controlled release of growth factors, making them a promising solution for treating diabetic wounds. Recently, researchers have focused on insulin, a hormone secreted by the human body to lower blood sugar levels, due to its interesting characteristics, such as supporting anti-inflammatory and proangiogenic processes and stimulating cell migration and proper proliferation. This review discusses the most important aspects of diabetes and diabetic wounds and traditional and innovative treatment methods, particularly hydrogel dressings used as systems for insulin delivery in response to glucose concentration.
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Affiliation(s)
- Agnieszka Kłapcia
- Academic Centre for Materials and Nanotechnology, AGH University of Krakow, 30-059 Krakow, Poland
| | - Patrycja Domalik-Pyzik
- Department of Biomaterials and Composites, Faculty of Materials Science and Ceramics, AGH University of Krakow, 30-059 Krakow, Poland
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Vasileva LA, Gaynanova GA, Romanova EA, Petrov KA, Feng C, Zakharova LY, Sinyashin OG. Supramolecular approach to the design of nanocarriers for antidiabetic drugs: targeted patient-friendly therapy. RUSSIAN CHEMICAL REVIEWS 2024; 93:RCR5150. [DOI: 10.59761/rcr5150] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Diabetes and its complications derived are among serious global health concerns that critically deteriorate the quality of life of patients and, in some cases, result in lethal outcome. Herein, general information on the pathogenesis, factors aggravating the course of the disease and drugs used for the treatment of two types of diabetes are briefly discussed. The aim of the review is to introduce supramolecular strategies that are currently being developed for the treatment of diabetes mellitus and that present a very effective alternative to chemical synthesis, allowing the fabrication of nanocontainers with switchable characteristics that meet the criteria of green chemistry. Particular attention is paid to organic (amphiphilic and polymeric) formulations, including those of natural origin, due to their biocompatibility, low toxicity, and bioavailability. The advantages and limitations of different nanosystems are discussed, with emphasis on their adaptivity to noninvasive administration routes.<br>The bibliography includes 378 references.
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Affiliation(s)
- L. A. Vasileva
- Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Kazan, Russian Federation
| | - G. A. Gaynanova
- Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Kazan, Russian Federation
| | - E. A. Romanova
- Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Kazan, Russian Federation
| | - K. A. Petrov
- Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Kazan, Russian Federation
| | - Ch. Feng
- Shanghai Jiao Tong University, Shanghai, China
| | - L. Ya. Zakharova
- Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Kazan, Russian Federation
| | - O. G. Sinyashin
- Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Kazan, Russian Federation
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Zhang S, Staples AE. Microfluidic-based systems for the management of diabetes. Drug Deliv Transl Res 2024; 14:2989-3008. [PMID: 38509342 PMCID: PMC11445324 DOI: 10.1007/s13346-024-01569-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/04/2024] [Indexed: 03/22/2024]
Abstract
Diabetes currently affects approximately 500 million people worldwide and is one of the most common causes of mortality in the United States. To diagnose and monitor diabetes, finger-prick blood glucose testing has long been used as the clinical gold standard. For diabetes treatment, insulin is typically delivered subcutaneously through cannula-based syringes, pens, or pumps in almost all type 1 diabetic (T1D) patients and some type 2 diabetic (T2D) patients. These painful, invasive approaches can cause non-adherence to glucose testing and insulin therapy. To address these problems, researchers have developed miniaturized blood glucose testing devices as well as microfluidic platforms for non-invasive glucose testing through other body fluids. In addition, glycated hemoglobin (HbA1c), insulin levels, and cellular biomechanics-related metrics have also been considered for microfluidic-based diabetes diagnosis. For the treatment of diabetes, insulin has been delivered transdermally through microdevices, mostly through microneedle array-based, minimally invasive injections. Researchers have also developed microfluidic platforms for oral, intraperitoneal, and inhalation-based delivery of insulin. For T2D patients, metformin, glucagon-like peptide 1 (GLP-1), and GLP-1 receptor agonists have also been delivered using microfluidic technologies. Thus far, clinical studies have been widely performed on microfluidic-based diabetes monitoring, especially glucose sensing, yet technologies for the delivery of insulin and other drugs to diabetic patients with microfluidics are still mostly in the preclinical stage. This article provides a concise review of the role of microfluidic devices in the diagnosis and monitoring of diabetes, as well as the delivery of pharmaceuticals to treat diabetes using microfluidic technologies in the recent literature.
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Affiliation(s)
- Shuyu Zhang
- Virginia Tech-Wake Forest School of Biomedical Engineering and Sciences, Blacksburg, VA, 24061, USA.
- Department of Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, VA, 24061, USA.
| | - Anne E Staples
- Virginia Tech-Wake Forest School of Biomedical Engineering and Sciences, Blacksburg, VA, 24061, USA
- Department of Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, VA, 24061, USA
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Al-Wraikat M, Abubaker MA, Liu Y, Shen XP, He Y, Li L, Liu Y. Label-free quantitative proteomic analysis of functional changes of goat milk whey proteins subject to heat treatments of ultra-high-temperature and the common low-temperature. Food Chem X 2024; 23:101691. [PMID: 39184313 PMCID: PMC11342887 DOI: 10.1016/j.fochx.2024.101691] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Revised: 07/17/2024] [Accepted: 07/21/2024] [Indexed: 08/27/2024] Open
Abstract
This work investigated the functional changes in whey proteins obtained from goat milk subject to various temperature treatments. Ultra-high temperature instantaneous sterilization (UHTIS) caused less damage than the common low-temperature, whereas spray-drying treatment had the opposite effect. A total of 426 proteins were identified in UHTIS and control treatment groups, including 386 common proteins and 16 and 14 unique proteins. The UHTIS treatment upregulated 55 whey proteins while down-regulated 98. The UHTIS-treated whey proteins may upregulate three metabolic pathways but downregulate one. Overall, UHTIS only slightly impacted the composition and functions of whey proteins from goat milk compared to the common low-temperature treatments.
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Affiliation(s)
- Majida Al-Wraikat
- College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an, 710119, China
| | - Mohamed Aamer Abubaker
- College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an, 710119, China
| | - Yingli Liu
- Hospital of Shaanxi Normal University, Shaanxi Normal University, Xi'an 710119, China
| | - Xi Ping Shen
- College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an, 710119, China
| | - Yu He
- College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an, 710119, China
| | - Linqiang Li
- College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an, 710119, China
| | - YongFeng Liu
- College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an, 710119, China
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Wong S, Brown AD, Abrahams AB, Nurzak AN, Eltaher HM, Sykes DA, Veprintsev DB, Fone KCF, Dixon JE, King MV. A Modified Cell-Penetrating Peptide Enhances Insulin and Oxytocin Delivery across an RPMI 2650 Nasal Epithelial Cell Barrier In Vitro. Pharmaceutics 2024; 16:1267. [PMID: 39458599 PMCID: PMC11510563 DOI: 10.3390/pharmaceutics16101267] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Revised: 09/23/2024] [Accepted: 09/26/2024] [Indexed: 10/28/2024] Open
Abstract
Background/Objectives: Peptide-based treatments represent an expanding area and require innovative approaches to enhance bioavailability. Combination with cell-penetrating peptides (CPPs) is an attractive strategy to improve non-invasive delivery across nasal epithelial barriers for systemic and direct nose-to-brain transport. We previously developed a modified CPP system termed Glycosaminoglycan-binding Enhanced Transduction (GET) that improves insulin delivery across gastrointestinal epithelium. It contains a membrane docking sequence to promote cellular interactions (P21), a cationic polyarginine domain to stimulate uptake (8R) and an endosomal escaping sequence to maximize availability for onward distribution (LK15). It is synthesized as a single 44-residue peptide (P21-LK15-8R; PLR). METHODS The current research used in vitro assays for a novel exploration of PLR's ability to improve the transport of two contrasting peptides, insulin (51 residues, net negative charge) and oxytocin (9 residues, weak positive charge) across an RPMI 2650 human nasal epithelial cell barrier cultured at the air-liquid interface. RESULTS PLR enhanced insulin transcytosis over a 6 h period by 7.8-fold when used at a 2:1 molar ratio of insulin/PLR (p < 0.0001 versus insulin alone). Enhanced oxytocin transcytosis (5-fold) occurred with a 1:10 ratio of oytocin/PLR (p < 0.01). Importantly, these were independent of any impact on transepithelial electrical resistance (TEER) or cell viability (p > 0.05). CONCLUSIONS We advocate the continued evaluation of insulin-PLR and oxytocin-PLR formulations, including longer-term assessments of ciliotoxicity and cytotoxicity in vitro followed by in vivo assessments of systemic and nose-to-brain delivery.
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Affiliation(s)
- Sara Wong
- Division of Physiology Pharmacology and Neuroscience, School of Life Sciences, University of Nottingham Medical School, Queen’s Medical Centre, Nottingham NG7 2UH, UK; (S.W.); (A.D.B.); (A.B.A.); (D.A.S.); (D.B.V.); (K.C.F.F.)
| | - Alexander D. Brown
- Division of Physiology Pharmacology and Neuroscience, School of Life Sciences, University of Nottingham Medical School, Queen’s Medical Centre, Nottingham NG7 2UH, UK; (S.W.); (A.D.B.); (A.B.A.); (D.A.S.); (D.B.V.); (K.C.F.F.)
| | - Abigail B. Abrahams
- Division of Physiology Pharmacology and Neuroscience, School of Life Sciences, University of Nottingham Medical School, Queen’s Medical Centre, Nottingham NG7 2UH, UK; (S.W.); (A.D.B.); (A.B.A.); (D.A.S.); (D.B.V.); (K.C.F.F.)
| | - An Nisaa Nurzak
- Regenerative Medicine and Cellular Therapies, School of Pharmacy, Biodiscovery Institute (BDI), University of Nottingham, University Park Campus, Nottingham NG7 2RD, UK; (A.N.N.); (H.M.E.); (J.E.D.)
| | - Hoda M. Eltaher
- Regenerative Medicine and Cellular Therapies, School of Pharmacy, Biodiscovery Institute (BDI), University of Nottingham, University Park Campus, Nottingham NG7 2RD, UK; (A.N.N.); (H.M.E.); (J.E.D.)
| | - David A. Sykes
- Division of Physiology Pharmacology and Neuroscience, School of Life Sciences, University of Nottingham Medical School, Queen’s Medical Centre, Nottingham NG7 2UH, UK; (S.W.); (A.D.B.); (A.B.A.); (D.A.S.); (D.B.V.); (K.C.F.F.)
| | - Dmitry B. Veprintsev
- Division of Physiology Pharmacology and Neuroscience, School of Life Sciences, University of Nottingham Medical School, Queen’s Medical Centre, Nottingham NG7 2UH, UK; (S.W.); (A.D.B.); (A.B.A.); (D.A.S.); (D.B.V.); (K.C.F.F.)
| | - Kevin C. F. Fone
- Division of Physiology Pharmacology and Neuroscience, School of Life Sciences, University of Nottingham Medical School, Queen’s Medical Centre, Nottingham NG7 2UH, UK; (S.W.); (A.D.B.); (A.B.A.); (D.A.S.); (D.B.V.); (K.C.F.F.)
| | - James E. Dixon
- Regenerative Medicine and Cellular Therapies, School of Pharmacy, Biodiscovery Institute (BDI), University of Nottingham, University Park Campus, Nottingham NG7 2RD, UK; (A.N.N.); (H.M.E.); (J.E.D.)
| | - Madeleine V. King
- Division of Physiology Pharmacology and Neuroscience, School of Life Sciences, University of Nottingham Medical School, Queen’s Medical Centre, Nottingham NG7 2UH, UK; (S.W.); (A.D.B.); (A.B.A.); (D.A.S.); (D.B.V.); (K.C.F.F.)
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12
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Bayrami S, Chamani M, JamaliMoghadamSiahkali S, SeyedAlinaghi S, Shirmard LR, Bayrami S, Javar HA, Ghahremani MH, Amini M, Tehrani MR, Shahsavari S, Dorkoosh FA. Preparation, Characterization and In vitro Evaluation of Insulin-PHBV Nanoparticles/Alginate Hydrogel Composite System for Prolonged Delivery of Insulin. J Pharm Sci 2024; 113:2552-2559. [PMID: 38508339 DOI: 10.1016/j.xphs.2024.03.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Revised: 03/14/2024] [Accepted: 03/14/2024] [Indexed: 03/22/2024]
Abstract
PURPOSE In the present study, biodegradable poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanoparticles (NPs) containing insulin were loaded in sodium alginate/jeffamine (ALG/jeff) hydrogel for prolonged delivery of insulin. The main aim of this work was to fabricate an efficient insulin delivery system to improve patient adherence by decreasing the repetition of injections. METHODS Swelling and morphological properties and crosslinking efficiency of ALG/jeff hydrogel were assessed. The composite hydrogel was prepared by adding PHBV NPs to ALG/jeff hydrogel concurrently with crosslinking process. The morphology and loading capacity of composite hydrogel were analyzed. RESULTS Circular dichroism measurement demonstrated that insulin remains stable following fabrication process. The release profile exhibited 54.6 % insulin release from composite hydrogel within 31 days with minor initial burst release equated to nanoparticles and hydrogels. MTT cell viability analysis was performed by applying L-929 cell line and no cytotoxic effect was observed. CONCLUSIONS Favorable results clearly introduced fabricated composite hydrogel as an excellent candidate for drug delivery systems and also paves the route for prolonged delivery systems of other proteins.
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Affiliation(s)
- Samane Bayrami
- Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Mehdi Chamani
- Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | | | - SeyedAhmad SeyedAlinaghi
- Iranian Research Center for HIV/AIDS, Iranian Institute for Reduction of High Risk Behaviors, Tehran University of Medical Sciences, Tehran, Iran
| | - Leila Rezaie Shirmard
- Department of Pharmaceutics, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Sepide Bayrami
- Islamic Azad University, North Tehran Branch, Faculty of Bioscience, Tehran, Iran
| | - Hamid Akbari Javar
- Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Hossein Ghahremani
- Department of Toxicology-Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohsen Amini
- Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Drug Design and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Morteza Rafiee Tehrani
- Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Shadab Shahsavari
- Chemical Engineering Department, Varamin-Pishva Branch, Islamic Azad University, Varamin, Iran
| | - Farid Abedin Dorkoosh
- Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Medical Biomaterial Research Centre (MBRC), Tehran University of Medical Sciences, Tehran 14399-56131, Iran.
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13
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Li H, Shi Y, Ding X, Zhen C, Lin G, Wang F, Tang B, Li X. Recent advances in transdermal insulin delivery technology: A review. Int J Biol Macromol 2024; 274:133452. [PMID: 38942414 DOI: 10.1016/j.ijbiomac.2024.133452] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2024] [Revised: 06/23/2024] [Accepted: 06/24/2024] [Indexed: 06/30/2024]
Abstract
Transdermal drug delivery refers to the administration of drugs through the skin, after which the drugs can directly act on or circulate through the body to the target organs or cells and avoid the first-pass metabolism in the liver and kidneys experienced by oral drugs, reducing the risk of drug poisoning. From the initial singular approach to transdermal drug delivery, there has been a shift toward combining multiple methods to enhance drug permeation efficiency and address the limitations of individual approaches. Technological advancements have also improved the accuracy of drug delivery. Optimizing insulin itself also enables its long-term release via needle-free injectors. In this review, the diverse transdermal delivery methods employed in insulin therapy and their respective advantages and limitations are discussed. By considering factors such as the principles of transdermal penetration, drug delivery efficiency, research progress, synergistic innovations among different methods, patient compliance, skin damage, and posttreatment skin recovery, a comprehensive evaluation is presented, along with prospects for potential novel combinatorial approaches. Furthermore, as insulin is a macromolecular drug, insights gained from its transdermal delivery may also serve as a valuable reference for the use of other macromolecular drugs for treatment.
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Affiliation(s)
- Heng Li
- School of Mechanical Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250353, China; Shandong Institute of Mechanical Design and Research, Jinan 250031, China
| | - Yanbin Shi
- School of Mechanical Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250353, China; Shandong Institute of Mechanical Design and Research, Jinan 250031, China; School of Arts and Design, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250353, China.
| | - Xinbing Ding
- School of Mechanical Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250353, China; Shandong Institute of Mechanical Design and Research, Jinan 250031, China.
| | - Chengdong Zhen
- School of Mechanical Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250353, China; Shandong Institute of Mechanical Design and Research, Jinan 250031, China
| | - Guimei Lin
- School of Pharmaceutical Science, Shandong University, Jinan 250012, China.
| | - Fei Wang
- School of Mechanical Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250353, China; Shandong Institute of Mechanical Design and Research, Jinan 250031, China.
| | - Bingtao Tang
- School of Mechanical Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250353, China; Shandong Institute of Mechanical Design and Research, Jinan 250031, China
| | - Xuelin Li
- School of Arts and Design, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250353, China
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14
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Muñoz-Galán H, Enshaei H, Silva JC, Esteves T, Ferreira FC, Casanovas J, Worch JC, Dove AP, Alemán C, Pérez-Madrigal MM. Electroresponsive Thiol-Yne Click-Hydrogels for Insulin Smart Delivery: Tackling Sustained Release and Leakage Control. ACS APPLIED POLYMER MATERIALS 2024; 6:8093-8104. [PMID: 39839886 PMCID: PMC11745422 DOI: 10.1021/acsapm.4c00911] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Revised: 05/31/2024] [Accepted: 06/20/2024] [Indexed: 01/23/2025]
Abstract
Diabetes is a metabolic disorder caused by the body's inability to produce or use insulin. Considering the figures projected by the World Health Organization, research on insulin therapy is crucial. Hence, we present a soft biointerface based on a thiol-yne poly(ethylene glycol) (PEG) click-hydrogel as an advanced treatment option to administrate insulin. Most importantly, the device is rendered electroactive by incorporating biocompatible poly(3,4-ethylenedioxythiophene) nanoparticles (PEDOT NPs) as conductive moieties to precisely control the release of insulin over an extended period through electrochemical stimulation (ES). The device has been carefully optimized on account of: (i) the main interactions established between PEDOT- and PEG-based moieties, which have been studied by density functional theory calculations, and reveal the choice of 4-arm PEG precursors as most suitable cross-linkers; and (ii) the concentration of PEDOT NPs in the device, which has been determined considering minimal interference with the gelation process, as well as the resulting morphological, mechanical, electrochemical, and cytocompatible properties of the PEG-based click-hydrogels. Finally, the management over insulin delivery through ES is verified in vitro, with released insulin being detected by high-performance liquid chromatography. Overall, our hydrogel-based device establishes a method for controlled insulin delivery with the potential for translation to other relevant bioelectronic applications.
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Affiliation(s)
- Helena Muñoz-Galán
- Departament
d’Enginyeria Química, Campus Diagonal Besòs (EEBE), Universitat Politècnica de Catalunya Barcelona
Tech, Av. Eduard Maristany
10-14, Barcelona 08019, Spain
- Barcelona
Research Center for Multiscale Science and Engineering, EEBE, Universitat Politècnica de Catalunya, C/Eduard Maristany 10-14, Barcelona 08019, Spain
| | - Hamidreza Enshaei
- Departament
d’Enginyeria Química, Campus Diagonal Besòs (EEBE), Universitat Politècnica de Catalunya Barcelona
Tech, Av. Eduard Maristany
10-14, Barcelona 08019, Spain
- Barcelona
Research Center for Multiscale Science and Engineering, EEBE, Universitat Politècnica de Catalunya, C/Eduard Maristany 10-14, Barcelona 08019, Spain
| | - João C. Silva
- iBB—Institute
for Bioengineering and Biosciences, Department of Bioengineering,Instituto Superior Técnico—Universidade
de Lisboa, Avenida Rovisco
Pais 1, Lisboa 1049-001, Portugal
- Associate
Laboratory i4HB—Institute for Health and Bioeconomy at Instituto
Superior Técnico, Universidade de
Lisboa, Avenida Rovisco
Pais 1, Lisboa 1049-001, Portugal
| | - Teresa Esteves
- iBB—Institute
for Bioengineering and Biosciences, Department of Bioengineering,Instituto Superior Técnico—Universidade
de Lisboa, Avenida Rovisco
Pais 1, Lisboa 1049-001, Portugal
- Associate
Laboratory i4HB—Institute for Health and Bioeconomy at Instituto
Superior Técnico, Universidade de
Lisboa, Avenida Rovisco
Pais 1, Lisboa 1049-001, Portugal
| | - Frederico Castelo Ferreira
- iBB—Institute
for Bioengineering and Biosciences, Department of Bioengineering,Instituto Superior Técnico—Universidade
de Lisboa, Avenida Rovisco
Pais 1, Lisboa 1049-001, Portugal
- Associate
Laboratory i4HB—Institute for Health and Bioeconomy at Instituto
Superior Técnico, Universidade de
Lisboa, Avenida Rovisco
Pais 1, Lisboa 1049-001, Portugal
| | - Jordi Casanovas
- Departament
de Química, Física i Ciències Ambientals i del
Sòl, Escola Politècnica Superior, Universitat de Lleida, C/Jaume II No. 69, Lleida E-25001, Spain
| | - Joshua C. Worch
- School of
Chemistry, University of Birmingham, University Rd W, Birmingham B152TT, U.K.
| | - Andrew P. Dove
- School of
Chemistry, University of Birmingham, University Rd W, Birmingham B152TT, U.K.
| | - Carlos Alemán
- Departament
d’Enginyeria Química, Campus Diagonal Besòs (EEBE), Universitat Politècnica de Catalunya Barcelona
Tech, Av. Eduard Maristany
10-14, Barcelona 08019, Spain
- Barcelona
Research Center for Multiscale Science and Engineering, EEBE, Universitat Politècnica de Catalunya, C/Eduard Maristany 10-14, Barcelona 08019, Spain
- Institute
for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology, Baldiri Reixac 10-12, Barcelona 08028, Spain
| | - Maria M. Pérez-Madrigal
- Departament
d’Enginyeria Química, Campus Diagonal Besòs (EEBE), Universitat Politècnica de Catalunya Barcelona
Tech, Av. Eduard Maristany
10-14, Barcelona 08019, Spain
- Barcelona
Research Center for Multiscale Science and Engineering, EEBE, Universitat Politècnica de Catalunya, C/Eduard Maristany 10-14, Barcelona 08019, Spain
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15
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Rimon MTI, Hasan MW, Hassan MF, Cesmeci S. Advancements in Insulin Pumps: A Comprehensive Exploration of Insulin Pump Systems, Technologies, and Future Directions. Pharmaceutics 2024; 16:944. [PMID: 39065641 PMCID: PMC11279469 DOI: 10.3390/pharmaceutics16070944] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2024] [Revised: 06/25/2024] [Accepted: 06/27/2024] [Indexed: 07/28/2024] Open
Abstract
Insulin pumps have transformed the way diabetes is managed by providing a more accurate and individualized method of delivering insulin, in contrast to conventional injection routines. This research explores the progression of insulin pumps, following their advancement from initial ideas to advanced contemporary systems. The report proceeds to categorize insulin pumps according to their delivery systems, specifically differentiating between conventional, patch, and implantable pumps. Every category is thoroughly examined, emphasizing its unique characteristics and capabilities. A comparative examination of commercially available pumps is provided to enhance informed decision making. This section provides a thorough analysis of important specifications among various brands and models. Considered factors include basal rate and bolus dosage capabilities, reservoir size, user interface, and compatibility with other diabetes care tools, such as continuous glucose monitoring (CGM) devices and so on. This review seeks to empower healthcare professionals and patients with the essential information to improve diabetes treatment via individualized pump therapy options. It provides a complete assessment of the development, categorization, and full specification comparisons of insulin pumps.
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Affiliation(s)
| | | | | | - Sevki Cesmeci
- Department of Mechanical Engineering, Georgia Southern University, Statesboro, GA 30458, USA
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16
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Huan Z, Li J, Luo Z, Yu Y, Li L. Hydrogel-Encapsulated Pancreatic Islet Cells as a Promising Strategy for Diabetic Cell Therapy. RESEARCH (WASHINGTON, D.C.) 2024; 7:0403. [PMID: 38966749 PMCID: PMC11221926 DOI: 10.34133/research.0403] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/11/2024] [Accepted: 05/16/2024] [Indexed: 07/06/2024]
Abstract
Islet transplantation has now become a promising treatment for insulin-deficient diabetes mellitus. Compared to traditional diabetes treatments, cell therapy can restore endogenous insulin supplementation, but its large-scale clinical application is impeded by donor shortages, immune rejection, and unsuitable transplantation sites. To overcome these challenges, an increasing number of studies have attempted to transplant hydrogel-encapsulated islet cells to treat diabetes. This review mainly focuses on the strategy of hydrogel-encapsulated pancreatic islet cells for diabetic cell therapy, including different cell sources encapsulated in hydrogels, encapsulation methods, hydrogel types, and a series of accessorial manners to improve transplantation outcomes. In addition, the formation and application challenges as well as prospects are also presented.
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Affiliation(s)
- Zhikun Huan
- Department of Endocrinology, Zhongda Hospital, School of Medicine,
Southeast University, Nanjing 210009, China
| | - Jingbo Li
- Department of Endocrinology, Zhongda Hospital, School of Medicine,
Southeast University, Nanjing 210009, China
| | - Zhiqiang Luo
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering,
Southeast University, Nanjing 210096, China
| | - Yunru Yu
- Pharmaceutical Sciences Laboratory,
Åbo Akademi University, Turku 20520, Finland
| | - Ling Li
- Department of Endocrinology, Zhongda Hospital, School of Medicine,
Southeast University, Nanjing 210009, China
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17
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Wong CYJ, Baldelli A, Hoyos CM, Tietz O, Ong HX, Traini D. Insulin Delivery to the Brain via the Nasal Route: Unraveling the Potential for Alzheimer's Disease Therapy. Drug Deliv Transl Res 2024; 14:1776-1793. [PMID: 38441832 PMCID: PMC11153287 DOI: 10.1007/s13346-024-01558-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/19/2024] [Indexed: 06/06/2024]
Abstract
This comprehensive review delves into the potential of intranasal insulin delivery for managing Alzheimer's Disease (AD) while exploring the connection between AD and diabetes mellitus (DM). Both conditions share features of insulin signalling dysregulation and oxidative stress that accelerate inflammatory response. Given the physiological barriers to brain drug delivery, including the blood-brain barrier, intranasal administration emerges as a non-invasive alternative. Notably, intranasal insulin has shown neuroprotective effects, impacting Aβ clearance, tau phosphorylation, and synaptic plasticity. In preclinical studies and clinical trials, intranasally administered insulin achieved rapid and extensive distribution throughout the brain, with optimal formulations exhibiting minimal systemic circulation. The detailed mechanism of insulin transport through the nose-to-brain pathway is elucidated in the review, emphasizing the role of olfactory and trigeminal nerves. Despite promising prospects, challenges in delivering protein drugs from the nasal cavity to the brain remain, including enzymes, tight junctions, mucociliary clearance, and precise drug deposition, which hinder its translation to clinical settings. The review encompasses a discussion of the strategies to enhance the intranasal delivery of therapeutic proteins, such as tight junction modulators, cell-penetrating peptides, and nano-drug carrier systems. Moreover, successful translation of nose-to-brain drug delivery necessitates a holistic understanding of drug transport mechanisms, brain anatomy, and nasal formulation optimization. To date, no intranasal insulin formulation has received regulatory approval for AD treatment. Future research should address challenges related to drug absorption, nasal deposition, and the long-term effects of intranasal insulin. In this context, the evaluation of administration devices for nose-to-brain drug delivery becomes crucial in ensuring precise drug deposition patterns and enhancing bioavailability.
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Affiliation(s)
- Chun Yuen Jerry Wong
- Respiratory Technology, Woolcock Institute of Medical Research, Sydney, NSW, 2037, Australia
- Faculty of Medicine and Health Sciences, Macquarie Medical School, Macquarie University, Sydney, NSW, 2109, Australia
| | - Alberto Baldelli
- Faculty of Land and Food Systems, The University of British Columbia, 2357 Main Mall, Vancouver, BC, V6T 1Z4, Canada
| | - Camilla M Hoyos
- Faculty of Medicine and Health Sciences, Macquarie Medical School, Macquarie University, Sydney, NSW, 2109, Australia
- CIRUS Centre for Sleep and Chronobiology, Woolcock Institute of Medical Research, Sydney, NSW, 2037, Australia
| | - Ole Tietz
- Dementia Research Centre, Faculty of Medicine and Health Sciences, Macquarie Medical School, Macquarie University, Sydney, NSW, 2109, Australia
| | - Hui Xin Ong
- Respiratory Technology, Woolcock Institute of Medical Research, Sydney, NSW, 2037, Australia.
- Faculty of Medicine and Health Sciences, Macquarie Medical School, Macquarie University, Sydney, NSW, 2109, Australia.
| | - Daniela Traini
- Respiratory Technology, Woolcock Institute of Medical Research, Sydney, NSW, 2037, Australia.
- Faculty of Medicine and Health Sciences, Macquarie Medical School, Macquarie University, Sydney, NSW, 2109, Australia.
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18
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Nizamani MM, Hughes AC, Zhang HL, Wang Y. Revolutionizing agriculture with nanotechnology: Innovative approaches in fungal disease management and plant health monitoring. THE SCIENCE OF THE TOTAL ENVIRONMENT 2024; 928:172473. [PMID: 38615773 DOI: 10.1016/j.scitotenv.2024.172473] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/03/2024] [Revised: 04/10/2024] [Accepted: 04/11/2024] [Indexed: 04/16/2024]
Abstract
Nanotechnology has emerged as a transformative force in modern agriculture, offering innovative solutions to address challenges related to fungal plant diseases and overall agricultural productivity. Specifically, the antifungal activities of metal, metal oxide, bio-nanoparticles, and polymer nanoparticles were examined, highlighting their unique mechanisms of action against fungal pathogens. Nanoparticles can be used as carriers for fungicides, offering advantages in controlled release, targeted delivery, and reduced environmental toxicity. Nano-pesticides and nano-fertilizers can enhance nutrient uptake, plant health, and disease resistance were explored. The development of nanosensors, especially those utilizing quantum dots and plasmonic nanoparticles, promises early and accurate detection of fungal pathogens, a crucial step in timely disease management. However, concerns about their potential toxic effects on non-target organisms, environmental impacts, and regulatory hurdles underscore the importance of rigorous research and impact assessments. The review concludes by emphasizing the significant prospects of nanotechnology in reshaping the future of agriculture but advocates for a balanced approach that prioritizes safety, sustainability, and environmental stewardship.
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Affiliation(s)
- Mir Muhammad Nizamani
- Department of Plant Pathology, College of Agriculture, Guizhou University, Guiyang 550025, China
| | - Alice C Hughes
- School of Biological Sciences, University of Hong Kong, China
| | - Hai-Li Zhang
- Sanya Nanfan Research Institute, Hainan Yazhou Bay Seed Laboratory, Sanya 572025, China
| | - Yong Wang
- Department of Plant Pathology, College of Agriculture, Guizhou University, Guiyang 550025, China.
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19
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Sabbagh F, Deshmukh AR, Choi Y, Kim BS. Effect of Microsphere Concentration on Catechin Release from Microneedle Arrays. ACS APPLIED MATERIALS & INTERFACES 2024; 16:28276-28289. [PMID: 38788676 DOI: 10.1021/acsami.4c06064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/26/2024]
Abstract
In this work, microspheres were developed by cross-linking glutaraldehyde in an aqueous gelatin solution with a surfactant and solvent. A poly(vinyl alcohol) (PVA) solution was produced and combined with catechin-loaded microspheres. Different microsphere concentrations (0%, 5%, 10%, and 15%) were applied to the PVA microneedles. The moisture content, particle size, swelling, and drug release percentage of microneedles were studied using various microsphere concentrations. Fourier transform infrared and scanning electron microscopy (SEM) investigations validated the structure of gelatin microspheres as well as their decoration in microneedles. The SEM scans revealed that spherical microspheres with a wrinkled and folded morphology were created, with no physical holes visible on the surface. The gelatin microspheres generated had a mean particle size of 20-30 μm. Ex vivo release analysis indicated that microneedles containing 10% microspheres released the most catechin, with 42.9% at 12 h and 84.4% at 24 h.
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Affiliation(s)
- Farzaneh Sabbagh
- Department of Chemical Engineering, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea
| | - Aarti R Deshmukh
- Department of Chemical Engineering, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea
| | - Yoseok Choi
- Department of Chemical Engineering, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea
| | - Beom Soo Kim
- Department of Chemical Engineering, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea
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20
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Gorantla A, Hall JTVE, Troidle A, Janjic JM. Biomaterials for Protein Delivery: Opportunities and Challenges to Clinical Translation. MICROMACHINES 2024; 15:533. [PMID: 38675344 PMCID: PMC11052476 DOI: 10.3390/mi15040533] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/14/2024] [Revised: 04/11/2024] [Accepted: 04/12/2024] [Indexed: 04/28/2024]
Abstract
The development of biomaterials for protein delivery is an emerging field that spans materials science, bioengineering, and medicine. In this review, we highlight the immense potential of protein-delivering biomaterials as therapeutic options and discuss the multifaceted challenges inherent to the field. We address current advancements and approaches in protein delivery that leverage stimuli-responsive materials, harness advanced fabrication techniques like 3D printing, and integrate nanotechnologies for greater targeting and improved stability, efficacy, and tolerability profiles. We also discuss the demand for highly complex delivery systems to maintain structural integrity and functionality of the protein payload. Finally, we discuss barriers to clinical translation, such as biocompatibility, immunogenicity, achieving reliable controlled release, efficient and targeted delivery, stability issues, scalability of production, and navigating the regulatory landscape for such materials. Overall, this review summarizes insights from a survey of the current literature and sheds light on the interplay between innovation and the practical implementation of biomaterials for protein delivery.
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Affiliation(s)
- Amogh Gorantla
- Department of Engineering, Wake Forest University, Winston-Salem, NC 27109, USA;
| | | | | | - Jelena M. Janjic
- School of Pharmacy, Duquesne University, Pittsburgh, PA 15282, USA;
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21
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Dai L, Wu F, Xiao Y, Liu Q, Meng M, Xi R, Yin Y. Template-Free Self-Assembly of Hollow Microtubular Covalent Organic Frameworks for Oral Delivery of Insulin. ACS APPLIED MATERIALS & INTERFACES 2024; 16:17891-17903. [PMID: 38546545 DOI: 10.1021/acsami.4c01165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/12/2024]
Abstract
Covalent organic frameworks (COFs) have demonstrated versatile application potential since their discovery. Although the structure of COFs is orderly arranged, the synthesis of controllable macrostructures still faces challenges. Herein, we report, to our knowledge, the first template-free self-assembled COF-18 Å hollow microtubule (MT-COF-18 Å) structure and its use for insulin delivery that exhibits high loading capacity, gastroresistance, and glucose-responsive properties. The hollow MT-COF-18 Å was achieved by a template-free method benefiting from the mixed solvents of mesitylene and dioxane. The formation mechanism and morphology changes with insulin loading and release were observed. In Caco-2 cells, the transferrin-coated system demonstrated enhanced insulin cellular uptake and transcellular transport, which indicated great potential for oral applications. Additionally, the composites presented sustained glycemic control and effective insulin blood concentrations without noticeable toxicity in diabetic rats. This work shows that hollow microtubular COFs hold great promise in loading and delivery of biomolecules.
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Affiliation(s)
- Lihui Dai
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300353, China
| | - Fang Wu
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300353, China
| | - Yi Xiao
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300353, China
| | - Qian Liu
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300353, China
| | - Meng Meng
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300353, China
| | - Rimo Xi
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300353, China
| | - Yongmei Yin
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300353, China
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22
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Kang Y, Xu L, Dong J, Yuan X, Ye J, Fan Y, Liu B, Xie J, Ji X. Programmed microalgae-gel promotes chronic wound healing in diabetes. Nat Commun 2024; 15:1042. [PMID: 38310127 PMCID: PMC10838327 DOI: 10.1038/s41467-024-45101-9] [Citation(s) in RCA: 85] [Impact Index Per Article: 85.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Accepted: 01/16/2024] [Indexed: 02/05/2024] Open
Abstract
Chronic diabetic wounds are at lifelong risk of developing diabetic foot ulcers owing to severe hypoxia, excessive reactive oxygen species (ROS), a complex inflammatory microenvironment, and the potential for bacterial infection. Here we develop a programmed treatment strategy employing live Haematococcus (HEA). By modulating light intensity, HEA can be programmed to perform a variety of functions, such as antibacterial activity, oxygen supply, ROS scavenging, and immune regulation, suggesting its potential for use in programmed therapy. Under high light intensity (658 nm, 0.5 W/cm2), green HEA (GHEA) with efficient photothermal conversion mediate wound surface disinfection. By decreasing the light intensity (658 nm, 0.1 W/cm2), the photosynthetic system of GHEA can continuously produce oxygen, effectively resolving the problems of hypoxia and promoting vascular regeneration. Continuous light irradiation induces astaxanthin (AST) accumulation in HEA cells, resulting in a gradual transformation from a green to red hue (RHEA). RHEA effectively scavenges excess ROS, enhances the expression of intracellular antioxidant enzymes, and directs polarization to M2 macrophages by secreting AST vesicles via exosomes. The living HEA hydrogel can sterilize and enhance cell proliferation and migration and promote neoangiogenesis, which could improve infected diabetic wound healing in female mice.
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Affiliation(s)
- Yong Kang
- Academy of Medical Engineering and Translational Medicine, Medical College, Tianjin University, Tianjin, 300072, China
| | - Lingling Xu
- Academy of Medical Engineering and Translational Medicine, Medical College, Tianjin University, Tianjin, 300072, China
| | - Jinrui Dong
- Academy of Medical Engineering and Translational Medicine, Medical College, Tianjin University, Tianjin, 300072, China
| | - Xue Yuan
- Academy of Medical Engineering and Translational Medicine, Medical College, Tianjin University, Tianjin, 300072, China
| | - Jiamin Ye
- Academy of Medical Engineering and Translational Medicine, Medical College, Tianjin University, Tianjin, 300072, China
| | - Yueyue Fan
- Academy of Medical Engineering and Translational Medicine, Medical College, Tianjin University, Tianjin, 300072, China
| | - Bing Liu
- Department of Disease Control and Prevention, Rocket Force Characteristic Medical Center, Beijing, 10088, China.
| | - Julin Xie
- Department of Burns, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China.
| | - Xiaoyuan Ji
- Academy of Medical Engineering and Translational Medicine, Medical College, Tianjin University, Tianjin, 300072, China.
- Medical College, Linyi University, Linyi, 276000, China.
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23
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Wu J, Roesger S, Jones N, Hu CMJ, Li SD. Cell-penetrating peptides for transmucosal delivery of proteins. J Control Release 2024; 366:864-878. [PMID: 38272399 DOI: 10.1016/j.jconrel.2024.01.038] [Citation(s) in RCA: 18] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Revised: 01/11/2024] [Accepted: 01/18/2024] [Indexed: 01/27/2024]
Abstract
Enabling non-invasive delivery of proteins across the mucosal barriers promises improved patient compliance and therapeutic efficacies. Cell-penetrating peptides (CPPs) are emerging as a promising and versatile tool to enhance protein and peptide permeation across various mucosal barriers. This review examines the structural and physicochemical attributes of the nasal, buccal, sublingual, and oral mucosa that hamper macromolecular delivery. Recent development of CPPs for overcoming those mucosal barriers for protein delivery is summarized and analyzed. Perspectives regarding current challenges and future research directions towards improving non-invasive transmucosal delivery of macromolecules for ultimate clinical translation are discussed.
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Affiliation(s)
- Jiamin Wu
- Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada
| | - Sophie Roesger
- Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada
| | - Natalie Jones
- Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada
| | - Che-Ming J Hu
- Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan
| | - Shyh-Dar Li
- Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
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24
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Adem MA, Decourt B, Sabbagh MN. Pharmacological Approaches Using Diabetic Drugs Repurposed for Alzheimer's Disease. Biomedicines 2024; 12:99. [PMID: 38255204 PMCID: PMC10813018 DOI: 10.3390/biomedicines12010099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Revised: 12/19/2023] [Accepted: 12/20/2023] [Indexed: 01/24/2024] Open
Abstract
Type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) are chronic, progressive disorders affecting the elderly, which fosters global healthcare concern with the growing aging population. Both T2DM and AD have been linked with increasing age, advanced glycosylation end products, obesity, and insulin resistance. Insulin resistance in the periphery is significant in the development of T2DM and it has been posited that insulin resistance in the brain plays a key role in AD pathogenesis, earning AD the name "type 3 diabetes". These clinical and epidemiological links between AD and T2DM have become increasingly pronounced throughout the years, and serve as a means to investigate the effects of antidiabetic therapies in AD, such as metformin, intranasal insulin, incretins, DPP4 inhibitors, PPAR-γ agonists, SGLT2 inhibitors. The majority of these drugs have shown benefit in preclinical trials, and have shown some promising results in clinical trials, with the improvement of cognitive faculties in participants with mild cognitive impairment and AD. In this review, we have summarize the benefits, risks, and conflicting data that currently exist for diabetic drugs being repurposed for the treatment of AD.
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Affiliation(s)
- Muna A. Adem
- Department of Neurology, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, 350 W. Thomas Rd., Phoenix, AZ 85013, USA
| | - Boris Decourt
- Department of Pharmacology and Neuroscience, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA;
| | - Marwan N. Sabbagh
- Department of Neurology, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, 350 W. Thomas Rd., Phoenix, AZ 85013, USA
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Luo D, Ni X, Yang H, Feng L, Chen Z, Bai L. A comprehensive review of advanced nasal delivery: Specially insulin and calcitonin. Eur J Pharm Sci 2024; 192:106630. [PMID: 37949195 DOI: 10.1016/j.ejps.2023.106630] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Revised: 10/18/2023] [Accepted: 11/08/2023] [Indexed: 11/12/2023]
Abstract
Peptide drugs through nasal mucous membrane, such as insulin and calcitonin have been widely used in the medical field. There are always two sides to a coin. One side, intranasal drug delivery can imitate the secretion pattern in human body, having advantages of physiological structure and convenient use. Another side, the low permeability of nasal mucosa, protease environment and clearance effect of nasal cilia hinder the intranasal absorption of peptide drugs. Researchers have taken multiple means to achieve faster therapeutic concentration, lower management dose, and fewer side effects for better nasal preparations. To improve the peptide drugs absorption, various strategies had been explored via the nasal mucosa route. In this paper, we reviewed the achievements of 18 peptide drugs in the past decade about the perspectives of the efficacy, mechanism of enhancing intranasal absorption and safety. The most studies were insulin and calcitonin. As a result, absorption enhancers, nanoparticles (NPs) and bio-adhesive system are the most widely used. Among them, chitosan (CS), cell penetrating peptides (CPPs), tight junction modulators (TJMs), soft NPs and gel/hydrogel are the most promising strategies. Moreover, two or three strategies can be combined to prepare drug vectors. In addition, spray freeze dried (SFD), self-emulsifying nano-system (SEN), and intelligent glucose reaction drug delivery system are new research directions in the future.
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Affiliation(s)
- Dan Luo
- Department of Pharmacy, Shantou Hospital of Traditional Chinese Medicine, Shantou, Guangdong, China
| | - Xiaoqing Ni
- Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Hao Yang
- Power China Chengdu Engineering Corporation Limited, Chengdu, Sichuan, China
| | - Lu Feng
- Department of Emergency, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan, China.
| | - Zhaoqun Chen
- Department of Pharmacy, Shantou Hospital of Traditional Chinese Medicine, Shantou, Guangdong, China.
| | - Lan Bai
- Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China; The State Key Laboratory of Southwestern Chinese Medicine Resources, Department of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
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26
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Fan L, Huang J, Ma S. Recent advances in delivery of transdermal nutrients: A review. Exp Dermatol 2024; 33:e14966. [PMID: 37897113 DOI: 10.1111/exd.14966] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Revised: 10/04/2023] [Accepted: 10/13/2023] [Indexed: 10/29/2023]
Abstract
Nutrients provide vital functions in the body for sustained health, which have been shown to be related to the incidence, prevention and treatment of disease. However, limited bioavailability, loss of targeting specificity and the increased hepatic metabolism limit the utilization of nutrients. In this review, we highlight transdermal absorption of nutrients, which represents an opportunity to allow great use of many nutrients with promising human health benefits. Moreover, we describe how the various types of permeation enhancers are increasingly exploited for transdermal nutrient delivery. Chemical penetration enhancers, carrier systems and physical techniques for transdermal nutrient delivery are described, with a focus on combinatorial approaches. Although there are many carrier systems and physical techniques currently in development, with some tools currently in advanced clinical trials, relatively few products have achieved full translation to clinical practice. Challenges and further developments of these tools are discussed here in this review. This review will be useful to researchers interested in transdermal applications of permeation enhancers for the efficient delivery of nutrients, providing a reference for supporting the need to take more account of specific nutritional needs in specific states.
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Affiliation(s)
- Ling Fan
- College of Agriculture, Henan University, Kaifeng, China
| | - Jihong Huang
- College of Agriculture, Henan University, Kaifeng, China
- Food and Pharmacy College, Xuchang University, Xuchang, China
- College of Food Science and Engineering, Henan University of Technology, Zhengzhou, China
| | - Sen Ma
- College of Agriculture, Henan University, Kaifeng, China
- College of Food Science and Engineering, Henan University of Technology, Zhengzhou, China
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27
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Wang X, Sun H, Mu T. Materials and structure of polysaccharide-based delivery carriers for oral insulin: A review. Carbohydr Polym 2024; 323:121364. [PMID: 37940264 DOI: 10.1016/j.carbpol.2023.121364] [Citation(s) in RCA: 14] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2023] [Revised: 08/24/2023] [Accepted: 09/02/2023] [Indexed: 11/10/2023]
Abstract
Diabetes mellitus is a chronic metabolic disease that affects >500 million patients worldwide. Subcutaneous injection of insulin is the most effective treatment at present. However, regular needle injections will cause pain, inflammation, and other adverse consequences. In recent years, significant progress has been made in non-injectable insulin preparations. Oral administration is the best way of administration due to its simplicity, convenience, and good patient compliance. However, oral insulin delivery is hindered by many physiological barriers in the gastrointestinal tract, resulting in the low relative bioavailability of direct oral insulin delivery. To improve the relative bioavailability, a variety of insulin delivery vectors have been developed. Polysaccharides are used to achieve safe and effective insulin loading due to their excellent biocompatibility and protein affinity. The functional characteristics of polysaccharide-based delivery carriers, such as pH responsiveness, mucosal adhesion, and further functionalization modifications, enhance the gastrointestinal absorption and bioavailability of insulin. This paper reviews the materials and structures of oral insulin polysaccharide-based carriers, providing ideas for further improving the relative bioavailability of oral insulin.
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Affiliation(s)
- Xinran Wang
- Laboratory of Food Chemistry and Nutrition Science, Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Key Laboratory of Agro-Products Processing, Ministry of Agriculture and Rural Affairs, No. 2 Yuan Ming Yuan West Road, Haidian District, P.O. Box 5109, Beijing 100193, China
| | - Hongnan Sun
- Laboratory of Food Chemistry and Nutrition Science, Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Key Laboratory of Agro-Products Processing, Ministry of Agriculture and Rural Affairs, No. 2 Yuan Ming Yuan West Road, Haidian District, P.O. Box 5109, Beijing 100193, China.
| | - Taihua Mu
- Laboratory of Food Chemistry and Nutrition Science, Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Key Laboratory of Agro-Products Processing, Ministry of Agriculture and Rural Affairs, No. 2 Yuan Ming Yuan West Road, Haidian District, P.O. Box 5109, Beijing 100193, China.
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Sarangi M, Padhi S, Rath G. Non-Invasive Delivery of Insulin for Breaching Hindrances against Diabetes. Crit Rev Ther Drug Carrier Syst 2024; 41:1-64. [PMID: 38608132 DOI: 10.1615/critrevtherdrugcarriersyst.2023048197] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/14/2024]
Abstract
Insulin is recognized as a crucial weapon in managing diabetes. Subcutaneous (s.c.) injections are the traditional approach for insulin administration, which usually have many limitations. Numerous alternative (non-invasive) slants through different routes have been explored by the researchers for making needle-free delivery of insulin for attaining its augmented absorption as well as bioavailability. The current review delineating numerous pros and cons of several novel approaches of non-invasive insulin delivery by overcoming many of their hurdles. Primary information on the topic was gathered by searching scholarly articles from PubMed added with extraction of data from auxiliary manuscripts. Many approaches (discussed in the article) are meant for the delivery of a safe, effective, stable, and patient friendly administration of insulin via buccal, oral, inhalational, transdermal, intranasal, ocular, vaginal and rectal routes. Few of them have proven their clinical efficacy for maintaining the glycemic levels, whereas others are under the investigational pipe line. The developed products are comprising of many advanced micro/nano composite technologies and few of them might be entering into the market in near future, thereby garnishing the hopes of millions of diabetics who are under the network of s.c. insulin injections.
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Affiliation(s)
| | - Sasmita Padhi
- Department of Pharmaceutics, Amity Institute of Pharmacy, Amity University, Malhaur Railway Station Road, Gomti Nagar, Lucknow, Uttar Pradesh, Pin-201313, India
| | - Goutam Rath
- Department of Pharmaceutics, School of Pharmaceutical Sciences, Siksha 'O' Anusandhan University, Bhubaneswar-751030, Odisha, India
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Li YH, Cheng YC, Liu HC, Wu J, Lee IT. Depressive Symptoms Associated with Peripheral Artery Disease and Predicting Mortality in Type 2 Diabetes. Biomedicines 2023; 12:29. [PMID: 38275390 PMCID: PMC10813585 DOI: 10.3390/biomedicines12010029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Revised: 12/18/2023] [Accepted: 12/19/2023] [Indexed: 01/27/2024] Open
Abstract
This retrospective cohort study aimed to assess the mortality risk in patients with type 2 diabetes mellitus (DM) by screening for depressive symptoms and peripheral artery disease (PAD). We enrolled patients aged ≥60 years who had undergone assessments of both the ankle-brachial index (ABI) and the five-item Geriatric Depression Scale (GDS-5). PAD and depression were defined as ABI ≤ 0.90 and GDS-5 ≥ 1, respectively. The primary endpoint was total mortality. In 1673 enrolled patients, the prevalence of PAD was higher in those with depression than in those without depression (8.9% vs. 5.7%, p = 0.021). After a median follow-up of 56.6 months (interquartile range: 47.0-62.3 months), a total of 168 (10.0%) deaths occurred. The patients in the depression and PAD subgroup had the highest hazard ratio of mortality, followed by the PAD without depression subgroup and the depression without PAD subgroup (2.209, 95%CI: 1.158-4.217; 1.958, 95%CI: 1.060-3.618; and 1.576, 95%CI: 1.131-2.196; respectively) in comparison to the patients without depression and PAD after adjustment for associated factors. In conclusion, a combination of depression and PAD predicted the highest mortality risk. Screening for depression and PAD is recommended in patients aged ≥60 years with type 2 DM.
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Affiliation(s)
- Yu-Hsuan Li
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 40705, Taiwan; (Y.-H.L.); (Y.-C.C.); (J.W.)
- School of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan
- Department of Computer Science & Information Engineering, National Taiwan University, Taipei 10617, Taiwan
| | - Yu-Cheng Cheng
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 40705, Taiwan; (Y.-H.L.); (Y.-C.C.); (J.W.)
- School of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan
- Institute of Biomedical Sciences, National Chung Hsing University, Taichung 40227, Taiwan
| | - Hsiu-Chen Liu
- Department of Nursing, Taichung Veterans General Hospital, Taichung 40705, Taiwan;
| | - Junyi Wu
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 40705, Taiwan; (Y.-H.L.); (Y.-C.C.); (J.W.)
| | - I-Te Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 40705, Taiwan; (Y.-H.L.); (Y.-C.C.); (J.W.)
- School of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan
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Sun HY, Lin XY. Genetic perspectives on childhood monogenic diabetes: Diagnosis, management, and future directions. World J Diabetes 2023; 14:1738-1753. [PMID: 38222792 PMCID: PMC10784795 DOI: 10.4239/wjd.v14.i12.1738] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2023] [Revised: 10/10/2023] [Accepted: 11/14/2023] [Indexed: 12/14/2023] Open
Abstract
Monogenic diabetes is caused by one or even more genetic variations, which may be uncommon yet have a significant influence and cause diabetes at an early age. Monogenic diabetes affects 1 to 5% of children, and early detection and gene-tically focused treatment of neonatal diabetes and maturity-onset diabetes of the young can significantly improve long-term health and well-being. The etiology of monogenic diabetes in childhood is primarily attributed to genetic variations affecting the regulatory genes responsible for beta-cell activity. In rare instances, mutations leading to severe insulin resistance can also result in the development of diabetes. Individuals diagnosed with specific types of monogenic diabetes, which are commonly found, can transition from insulin therapy to sulfonylureas, provided they maintain consistent regulation of their blood glucose levels. Scientists have successfully devised materials and methodologies to distinguish individuals with type 1 or 2 diabetes from those more prone to monogenic diabetes. Genetic screening with appropriate findings and interpretations is essential to establish a prognosis and to guide the choice of therapies and management of these interrelated ailments. This review aims to design a comprehensive literature summarizing genetic insights into monogenetic diabetes in children and adolescents as well as summarizing their diagnosis and mana-gement.
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Affiliation(s)
- Hong-Yan Sun
- Department of Endocrine and Metabolic Diseases, Yantaishan Hospital, Yantai 264003, Shandong Province, China
| | - Xiao-Yan Lin
- Department of Endocrine and Metabolic Diseases, Yantaishan Hospital, Yantai 264003, Shandong Province, China
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Mansoor S, Adeyemi SA, Kondiah PPD, Choonara YE. A Closed Loop Stimuli-Responsive Concanavalin A-Loaded Chitosan-Pluronic Hydrogel for Glucose-Responsive Delivery of Short-Acting Insulin Prototyped in RIN-5F Pancreatic Cells. Biomedicines 2023; 11:2545. [PMID: 37760986 PMCID: PMC10526345 DOI: 10.3390/biomedicines11092545] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2023] [Revised: 09/12/2023] [Accepted: 09/13/2023] [Indexed: 09/29/2023] Open
Abstract
The optimal treatment of diabetes (in particular, type 1 diabetes-T1D) remains a challenge. Closed-loop systems (implants/inserts) provide significant advantages for glucose responsivity and providing real-time sustained release of rapid-acting insulin. Concanavalin A (ConA), a glucose affinity agent, has been used to design closed-loop insulin delivery systems but not without significant risk of leakage of ConA from the matrices and poor mechanical strength of the hydrogels impacting longevity and control of insulin release. Therefore, this work focused on employing a thermoresponsive co-forming matrix between Pluronic F-127 (PL) and structurally robust chitosan (CHT) via EDC/NHS coupling (i.e., covalent linkage of -NH2 from CHT and ConA to the -COOH of PL). The system was characterized for its chemical structure stability and integrity (FTIR, XRD and TGA), injectability, rheological parameters and hydrogel morphology (Texture Analysis, Elastosens TM Bio2 and SEM). The prepared hydrogels demonstrated shear-thinning for injectability with a maximum force of 4.9 ± 8.3 N in a 26G needle with sol-gel transitioning from 25 to 38 °C. The apparent yield stress value of the hydrogel was determined to be 67.47 Pa. The insulin loading efficiency within the hydrogel matrix was calculated to be 46.8%. Insulin release studies revealed glucose responsiveness in simulated glycemic media (4 and 10 mg/mL) over 7 days (97%) (305 nm via fluorescence spectrophotometry). The MTT studies were performed over 72 h on RIN-5F pancreatic cells with viability results >80%. Results revealed that the thermoresponsive hydrogel is a promising alternative to current closed-loop insulin delivery systems.
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Affiliation(s)
| | | | | | - Yahya E. Choonara
- Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Science, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2093, South Africa; (S.M.); (S.A.A.); (P.P.D.K.)
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Dascalu AM, Serban D, Tanasescu D, Vancea G, Cristea BM, Stana D, Nicolae VA, Serboiu C, Tribus LC, Tudor C, Georgescu A, Tudosie MS, Costea DO, Bratu DG. The Value of White Cell Inflammatory Biomarkers as Potential Predictors for Diabetic Retinopathy in Type 2 Diabetes Mellitus (T2DM). Biomedicines 2023; 11:2106. [PMID: 37626602 PMCID: PMC10452280 DOI: 10.3390/biomedicines11082106] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Revised: 07/19/2023] [Accepted: 07/24/2023] [Indexed: 08/27/2023] Open
Abstract
The pathogenesis of diabetic retinopathy is still challenging, with recent evidence proving the key role of inflammation in the damage of the retinal neurovascular unit. This study aims to investigate the predictive value of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic inflammation index (SII) for diabetic retinopathy (DR) and its severity. We performed a retrospective study on 129 T2DM patients, divided into three groups: without retinopathy (NDR), non-proliferative DR (NPDR), and proliferative DR (PDR). NLR, MLR, and SII were significantly higher in the PDR group when compared to NDR and NPDR (3.2 ± 1.6 vs. 2.4 ± 0.9 and 2.4 ± 1.1; p = 0.005; 0.376 ± 0.216 vs. 0.269 ± 0.083 and 0.275 ± 0.111, p = 0.001; 754.4 ± 514.4 vs. 551.5 ± 215.1 and 560.3 ± 248.6, p = 0.013, respectively). PDR was correlated with serum creatinine (OR: 2.551), NLR (OR: 1.645), MPV (OR: 1.41), and duration of diabetes (OR: 1.301). Logistic regression analysis identified three predictive models with very good discrimination power for PDR (AUC ROC of 0.803, 0.809, and 0.830, respectively): combining duration of diabetes with NLR, MLR, and, respectively, PLR, MPV, and serum creatinine. NLR, MPV, SII, and LMR were associated with PDR and could be useful when integrated into comprehensive risk prediction models.
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Affiliation(s)
- Ana Maria Dascalu
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy Bucharest, 020021 Bucharest, Romania (G.V.)
- Ophthalmology Department, Emergency University Hospital Bucharest, 050098 Bucharest, Romania
| | - Dragos Serban
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy Bucharest, 020021 Bucharest, Romania (G.V.)
| | - Denisa Tanasescu
- Department of Nursing and Dentistry, Faculty of General Medicine, ‘Lucian Blaga’ University of Sibiu, 550169 Sibiu, Romania
| | - Geta Vancea
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy Bucharest, 020021 Bucharest, Romania (G.V.)
| | - Bogdan Mihai Cristea
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy Bucharest, 020021 Bucharest, Romania (G.V.)
| | - Daniela Stana
- Ophthalmology Department, Emergency University Hospital Bucharest, 050098 Bucharest, Romania
| | - Vanessa Andrada Nicolae
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy Bucharest, 020021 Bucharest, Romania (G.V.)
- Ophthalmology Department, Emergency University Hospital Bucharest, 050098 Bucharest, Romania
| | - Crenguta Serboiu
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy Bucharest, 020021 Bucharest, Romania (G.V.)
| | - Laura Carina Tribus
- Faculty of Dental Medicine, Carol Davila University of Medicine and Pharmacy Bucharest, 020021 Bucharest, Romania
| | - Corneliu Tudor
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy Bucharest, 020021 Bucharest, Romania (G.V.)
| | - Adriana Georgescu
- Ophthalmology Department, Emergency University Hospital Bucharest, 050098 Bucharest, Romania
| | - Mihail Silviu Tudosie
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy Bucharest, 020021 Bucharest, Romania (G.V.)
| | - Daniel Ovidiu Costea
- Faculty of Medicine, Ovidius University Constanta, 900470 Constanta, Romania
- General Surgery Department, Emergency County Hospital Constanta, 900591 Constanta, Romania
| | - Dan Georgian Bratu
- Faculty of Medicine, University “Lucian Blaga”, 550169 Sibiu, Romania
- Department of Surgery, Emergency County Hospital Sibiu, 550245 Sibiu, Romania
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Cai L, Wang Y, Luo Z, Wang J, Ren H, Zhao Y. Designing self-triggered micro/milli devices for gastrointestinal tract drug delivery. Expert Opin Drug Deliv 2023; 20:1415-1425. [PMID: 37817636 DOI: 10.1080/17425247.2023.2269092] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Accepted: 10/06/2023] [Indexed: 10/12/2023]
Abstract
INTRODUCTION Self-triggered micro-/milli-devices (STMDs), which are artificial devices capable of responding to the surrounding environment and transferring external energy into kinetic energy, thus realizing autonomous movement, have come to the forefront as a powerful tool in cargo delivery via gastrointestinal tract. Urgent needs have been raised to overview the development of this area. AREAS COVERED We summarize the advancement of designing STMDs for delivery via gastrointestinal tract. We first give a brief overview on the opportunities and challenges of delivery via gastrointestinal tract involving gastric barriers and intestinal barriers. Then, emphasis is laid on the design and applications of STMDs for delivery via gastrointestinal tract. We focus on their morphological characteristics and function design, expounding their working mechanisms in the complex gastrointestinal tract. EXPERT OPINION Although with much progress in STMDs, there is still a huge gap between laboratory researches and clinical applications due to some limitations including latent digestive burden, sophisticated fabrication, unstable delivery, and so on. We give a discussion on the potential, challenges, and prospects of developing STMDs for delivery via gastrointestinal tract.
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Affiliation(s)
- Lijun Cai
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, School of Biological Science and Medical Engineering, Southeast University, Nanjing, China
| | | | - Zhiqiang Luo
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, School of Biological Science and Medical Engineering, Southeast University, Nanjing, China
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Khan IU, Raiaan MAK, Fatema K, Azam S, Rashid RU, Mukta SH, Jonkman M, De Boer F. A Computer-Aided Diagnostic System to Identify Diabetic Retinopathy, Utilizing a Modified Compact Convolutional Transformer and Low-Resolution Images to Reduce Computation Time. Biomedicines 2023; 11:1566. [PMID: 37371661 DOI: 10.3390/biomedicines11061566] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2023] [Revised: 05/23/2023] [Accepted: 05/26/2023] [Indexed: 06/29/2023] Open
Abstract
Diabetic retinopathy (DR) is the foremost cause of blindness in people with diabetes worldwide, and early diagnosis is essential for effective treatment. Unfortunately, the present DR screening method requires the skill of ophthalmologists and is time-consuming. In this study, we present an automated system for DR severity classification employing the fine-tuned Compact Convolutional Transformer (CCT) model to overcome these issues. We assembled five datasets to generate a more extensive dataset containing 53,185 raw images. Various image pre-processing techniques and 12 types of augmentation procedures were applied to improve image quality and create a massive dataset. A new DR-CCTNet model is proposed. It is a modification of the original CCT model to address training time concerns and work with a large amount of data. Our proposed model delivers excellent accuracy even with low-pixel images and still has strong performance with fewer images, indicating that the model is robust. We compare our model's performance with transfer learning models such as VGG19, VGG16, MobileNetV2, and ResNet50. The test accuracy of the VGG19, ResNet50, VGG16, and MobileNetV2 were, respectively, 72.88%, 76.67%, 73.22%, and 71.98%. Our proposed DR-CCTNet model to classify DR outperformed all of these with a 90.17% test accuracy. This approach provides a novel and efficient method for the detection of DR, which may lower the burden on ophthalmologists and expedite treatment for patients.
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Affiliation(s)
- Inam Ullah Khan
- Health Informatics Research Lab, Department of Computer Science and Engineering, Daffodil International University, Dhaka 1207, Bangladesh
| | | | - Kaniz Fatema
- Health Informatics Research Lab, Department of Computer Science and Engineering, Daffodil International University, Dhaka 1207, Bangladesh
| | - Sami Azam
- Faculty of Science and Technology, Charles Darwin University, Darwin, NT 0909, Australia
| | - Rafi Ur Rashid
- Department of Computer Science and Engineering, Penn State University, State College, PA 16801, USA
| | - Saddam Hossain Mukta
- Department of Computer Science and Engineering, United International University, Dhaka 1212, Bangladesh
| | - Mirjam Jonkman
- Faculty of Science and Technology, Charles Darwin University, Darwin, NT 0909, Australia
| | - Friso De Boer
- Faculty of Science and Technology, Charles Darwin University, Darwin, NT 0909, Australia
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Yuce-Erarslan E, Domb AAJ, Kasem H, Uversky VN, Coskuner-Weber O. Intrinsically Disordered Synthetic Polymers in Biomedical Applications. Polymers (Basel) 2023; 15:polym15102406. [PMID: 37242981 DOI: 10.3390/polym15102406] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Revised: 04/29/2023] [Accepted: 05/18/2023] [Indexed: 05/28/2023] Open
Abstract
In biology and medicine, intrinsically disordered synthetic polymers bio-mimicking intrinsically disordered proteins, which lack stable three-dimensional structures, possess high structural/conformational flexibility. They are prone to self-organization and can be extremely useful in various biomedical applications. Among such applications, intrinsically disordered synthetic polymers can have potential usage in drug delivery, organ transplantation, artificial organ design, and immune compatibility. The designing of new syntheses and characterization mechanisms is currently required to provide the lacking intrinsically disordered synthetic polymers for biomedical applications bio-mimicked using intrinsically disordered proteins. Here, we present our strategies for designing intrinsically disordered synthetic polymers for biomedical applications based on bio-mimicking intrinsically disordered proteins.
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Affiliation(s)
- Elif Yuce-Erarslan
- Chemical Engineering, Istanbul University-Cerrahpasa, Avcilar, Istanbul 34320, Turkey
| | - Abraham Avi J Domb
- School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel
| | - Haytam Kasem
- Azrieli College of Engineering, 26 Ya'akov Schreiboim Street, Jerusalem 9103501, Israel
| | - Vladimir N Uversky
- Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA
| | - Orkid Coskuner-Weber
- Molecular Biotechnology, Turkish-German University, Sahinkaya Caddesi, No. 106, Beykoz, Istanbul 34820, Turkey
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Nuzaiba PM, Gupta S, Gupta S, Jadhao SB. Synthesis of L-methionine-loaded chitosan nanoparticles for controlled release and their in vitro and in vivo evaluation. Sci Rep 2023; 13:7606. [PMID: 37164991 PMCID: PMC10172396 DOI: 10.1038/s41598-023-34448-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2023] [Accepted: 04/30/2023] [Indexed: 05/12/2023] Open
Abstract
Therapeutically popular controlled release-enabling technology has forayed into the nutrition sector. Polymer coated forms of L-methionine used in soy protein diets, and its intermediate metabolite, S-adenosyl-L-methionine, used in myriad of medical conditions have proved more efficacious over (highly catabolized) free forms. In this premier study, L-methionine-loaded chitosan nanoparticles (M-NPs) were synthesized using ionic gelation method and their efficacy was evaluated. Biophysical characterization of the NPs was done using a Nanopartica SZ 100 analyser, transmission electron microscopy, and Fourier transform infrared spectroscopy. The M-NPs were spherical and smooth and 218.9 ± 7.4 nm in size and in vitro testing confirmed the controlled release of methionine. A 60-days feeding trial in L. rohita fish fingerlings was conducted. A basal diet suboptimal (0.85%) in methionine was provided with one of the supplements as under: none (control), 0.8% chitosan NPs (0.8% NPs), 1.2% L-methionine (1.2% M) (crystalline free form), 0.6% M-NPs and 1.2% M-NPs. While the addition of 0.6% M-NPs to the basal diet complemented towards meeting the established dietary requirement and resulted in significantly highest (P < 0.05) growth and protein efficiency and sero-immunological test scores (serum total protein, serum globulin, serum albumin: globulin ratio, phagocytic respiratory burst/NBT reduction and lysozyme activity), 1.2% supplementation in either form (free or nano), for being 0.85% excess, was counterproductive. Liver transaminases and dehydrogenases corroborated enhanced growth. It was inferred that part of the methionine requirement in nano form (M-NPs) can confer intended performance and health benefits in animals relying on plant proteins-based diets limiting in this essential amino acid. The study also paves the way for exploring chitosan NPs-based sustained delivery of amino acids in human medical conditions.
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Affiliation(s)
- Pallath Muhammed Nuzaiba
- Division of Fish Nutrition, Biochemistry and Physiology, Central Institute of Fisheries Education, Mumbai, Maharashtra, 400061, India
| | - Subodh Gupta
- Division of Fish Nutrition, Biochemistry and Physiology, Central Institute of Fisheries Education, Mumbai, Maharashtra, 400061, India.
| | - Shobha Gupta
- Department of Biotechnology, Annasaheb Vartak College of Arts, Commerce, Science, Vasai West, Mumbai, 401202, India
| | - Sanjay Balkrishna Jadhao
- Division of Fish Nutrition, Biochemistry and Physiology, Central Institute of Fisheries Education, Mumbai, Maharashtra, 400061, India.
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de Lemos Vasconcelos Silva E, de Jesus Oliveira AC, de Carvalho Moreira LMC, Silva-Filho EC, Wanderley AG, de La Roca Soares MF, Soares-Sobrinho JL. Insulin-loaded nanoparticles based on acetylated cashew gum/chitosan complexes for oral administration and diabetes treatment. Int J Biol Macromol 2023; 242:124737. [PMID: 37148931 DOI: 10.1016/j.ijbiomac.2023.124737] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 04/28/2023] [Accepted: 05/01/2023] [Indexed: 05/08/2023]
Abstract
Insulin is one of the most important drugs in the clinical treatment of diabetes. There is growing interest in oral insulin administration as it mimics the physiological pathway and potentially reduces side effects associated with subcutaneous injection. In this study, a nanoparticulate system was developed using acetylated cashew gum (ACG) and chitosan by the polyelectrolyte complexation method, for oral administration of insulin. The nanoparticles were characterized by size, zeta potential and encapsulation efficiency (EE%). And they had a particle size of 460 ± 11.0 nm, PDI of 0.2 ± 0.021, zeta potential of 30.6 ± 0.48 mV, and an EE% of 52.5 %. Cytotoxicity assays were performed for HT-29 cell lines. It was observed that ACG and nanoparticles did not have a significant effect on cell viability, verifying their biocompatibility. Hypoglycemic effects of the formulation were analyzed in vivo, noting that the nanoparticles reduced blood glucose by 51.0 % of baseline levels after 12 h, not inducing signs of toxicity or death. Biochemical and hematological profiles were not clinically modified. Histological study indicated no signs of toxicity. Results showed that the nanostructured system presented itself as a potential vehicle for oral insulin release.
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Affiliation(s)
- Eliadna de Lemos Vasconcelos Silva
- Quality Control Core of Medicines and Correlates - NCQMC, Department of Pharmaceutical Sciences, Federal University of Pernambuco, Recife, PE, Brazil
| | - Antônia Carla de Jesus Oliveira
- Quality Control Core of Medicines and Correlates - NCQMC, Department of Pharmaceutical Sciences, Federal University of Pernambuco, Recife, PE, Brazil
| | | | - Edson C Silva-Filho
- Interdisciplinary Laboratory for Advanced Materials - LIMAV, Federal University of Piaui, Teresina, PI, Brazil
| | | | - Monica Felts de La Roca Soares
- Quality Control Core of Medicines and Correlates - NCQMC, Department of Pharmaceutical Sciences, Federal University of Pernambuco, Recife, PE, Brazil
| | - José Lamartine Soares-Sobrinho
- Quality Control Core of Medicines and Correlates - NCQMC, Department of Pharmaceutical Sciences, Federal University of Pernambuco, Recife, PE, Brazil.
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Behzadifar S, Barras A, Plaisance V, Pawlowski V, Szunerits S, Abderrahmani A, Boukherroub R. Polymer-Based Nanostructures for Pancreatic Beta-Cell Imaging and Non-Invasive Treatment of Diabetes. Pharmaceutics 2023; 15:pharmaceutics15041215. [PMID: 37111699 PMCID: PMC10143373 DOI: 10.3390/pharmaceutics15041215] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Revised: 04/01/2023] [Accepted: 04/07/2023] [Indexed: 04/29/2023] Open
Abstract
Diabetes poses major economic, social, and public health challenges in all countries worldwide. Besides cardiovascular disease and microangiopathy, diabetes is a leading cause of foot ulcers and lower limb amputations. With the continued rise of diabetes prevalence, it is expected that the future burden of diabetes complications, early mortality, and disabilities will increase. The diabetes epidemic is partly caused by the current lack of clinical imaging diagnostic tools, the timely monitoring of insulin secretion and insulin-expressing cell mass (beta (β)-cells), and the lack of patients' adherence to treatment, because some drugs are not tolerated or invasively administrated. In addition to this, there is a lack of efficient topical treatment capable of stopping the progression of disabilities, in particular for treating foot ulcers. In this context, polymer-based nanostructures garnered significant interest due to their tunable physicochemical characteristics, rich diversity, and biocompatibility. This review article emphasizes the last advances and discusses the prospects in the use of polymeric materials as nanocarriers for β-cell imaging and non-invasive drug delivery of insulin and antidiabetic drugs in the management of blood glucose and foot ulcers.
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Affiliation(s)
- Shakila Behzadifar
- Univ. Lille, CNRS, Centrale Lille, Univ. Polytechnique Hauts-de-France, UMR 8520, IEMN, F-59000 Lille, France
| | - Alexandre Barras
- Univ. Lille, CNRS, Centrale Lille, Univ. Polytechnique Hauts-de-France, UMR 8520, IEMN, F-59000 Lille, France
| | - Valérie Plaisance
- Univ. Lille, CNRS, Centrale Lille, Univ. Polytechnique Hauts-de-France, UMR 8520, IEMN, F-59000 Lille, France
| | - Valérie Pawlowski
- Univ. Lille, CNRS, Centrale Lille, Univ. Polytechnique Hauts-de-France, UMR 8520, IEMN, F-59000 Lille, France
| | - Sabine Szunerits
- Univ. Lille, CNRS, Centrale Lille, Univ. Polytechnique Hauts-de-France, UMR 8520, IEMN, F-59000 Lille, France
| | - Amar Abderrahmani
- Univ. Lille, CNRS, Centrale Lille, Univ. Polytechnique Hauts-de-France, UMR 8520, IEMN, F-59000 Lille, France
| | - Rabah Boukherroub
- Univ. Lille, CNRS, Centrale Lille, Univ. Polytechnique Hauts-de-France, UMR 8520, IEMN, F-59000 Lille, France
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Neag MA, Craciun AE, Inceu AI, Burlacu DE, Craciun CI, Buzoianu AD. Short-Chain Fatty Acids as Bacterial Enterocytes and Therapeutic Target in Diabetes Mellitus Type 2. Biomedicines 2022; 11:72. [PMID: 36672580 PMCID: PMC9855839 DOI: 10.3390/biomedicines11010072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 12/10/2022] [Accepted: 12/23/2022] [Indexed: 12/29/2022] Open
Abstract
Diabetes mellitus is a disease with multiple gastrointestinal symptoms (diarrhea or constipation, abdominal pain, bloating) whose pathogenesis is multifactorial. The most important of these factors is the enteric nervous system, also known as the "second brain"; a part of the peripheral nervous system capable of functioning independently of the central nervous system. Modulation of the enteric nervous system can be done by short-chain fatty acids, which are bacterial metabolites of the intestinal microbiota. In addition, these acids provide multiple benefits in diabetes, particularly by stimulating glucagon-like peptide 1 and insulin secretion. However, it is not clear what type of nutraceuticals (probiotics, prebiotics, and alimentary supplements) can be used to increase the amount of short-chain fatty acids and achieve the beneficial effects in diabetes. Thus, even if several studies demonstrate that the gut microbiota modulates the activity of the ENS, and thus, may have a positive effect in diabetes, further studies are needed to underline this effect. This review outlines the most recent data regarding the involvement of SCFAs as a disease modifying agent in diabetes mellitus type 2. For an in-depth understanding of the modulation of gut dysbiosis with SCFAs in diabetes, we provide an overview of the interplay between gut microbiota and ENS.
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Affiliation(s)
- Maria-Adriana Neag
- Department of Pharmacology, Toxicology and Clinical Pharmacology, Iuliu Hatieganu University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania
| | - Anca-Elena Craciun
- Department of Diabetes and Nutrition Diseases, Iuliu Hatieganu University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania
| | - Andreea-Ioana Inceu
- Department of Pharmacology, Toxicology and Clinical Pharmacology, Iuliu Hatieganu University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania
| | - Diana-Elena Burlacu
- Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Cristian-Ioan Craciun
- Department of Pharmacology, Toxicology and Clinical Pharmacology, Iuliu Hatieganu University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania
| | - Anca-Dana Buzoianu
- Department of Pharmacology, Toxicology and Clinical Pharmacology, Iuliu Hatieganu University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania
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Liu Y, Su G, Zhang R, Dai R, Li Z. Nanomaterials-Functionalized Hydrogels for the Treatment of Cutaneous Wounds. Int J Mol Sci 2022; 24:336. [PMID: 36613778 PMCID: PMC9820076 DOI: 10.3390/ijms24010336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 12/17/2022] [Accepted: 12/21/2022] [Indexed: 12/28/2022] Open
Abstract
Hydrogels have been utilized extensively in the field of cutaneous wound treatment. The introduction of nanomaterials (NMs), which are a big category of materials with diverse functionalities, can endow the hydrogels with additional and multiple functions to meet the demand for a comprehensive performance in wound dressings. Therefore, NMs-functionalized hydrogels (NMFHs) as wound dressings have drawn intensive attention recently. Herein, an overview of reports about NMFHs for the treatment of cutaneous wounds in the past five years is provided. Firstly, fabrication strategies, which are mainly divided into physical embedding and chemical synthesis of the NMFHs, are summarized and illustrated. Then, functions of the NMFHs brought by the NMs are reviewed, including hemostasis, antimicrobial activity, conductivity, regulation of reactive oxygen species (ROS) level, and stimulus responsiveness (pH responsiveness, photo-responsiveness, and magnetic responsiveness). Finally, current challenges and future perspectives in this field are discussed with the hope of inspiring additional ideas.
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Affiliation(s)
- Yangkun Liu
- Institute of Engineering Medicine, School of Medical Technology, Beijing Institute of Technology, 5 South Zhongguancun Street, Haidian District, Beijing 100081, China
- Beijing Key Laboratory for Separation and Analysis in Biomedicine and Pharmaceuticals, Beijing Institute of Technology, 5 South Zhongguancun Street, Haidian District, Beijing 100081, China
| | - Gongmeiyue Su
- Institute of Engineering Medicine, School of Medical Technology, Beijing Institute of Technology, 5 South Zhongguancun Street, Haidian District, Beijing 100081, China
- Beijing Key Laboratory for Separation and Analysis in Biomedicine and Pharmaceuticals, Beijing Institute of Technology, 5 South Zhongguancun Street, Haidian District, Beijing 100081, China
| | - Ruoyao Zhang
- Institute of Engineering Medicine, School of Medical Technology, Beijing Institute of Technology, 5 South Zhongguancun Street, Haidian District, Beijing 100081, China
- Beijing Key Laboratory for Separation and Analysis in Biomedicine and Pharmaceuticals, Beijing Institute of Technology, 5 South Zhongguancun Street, Haidian District, Beijing 100081, China
| | - Rongji Dai
- Beijing Key Laboratory for Separation and Analysis in Biomedicine and Pharmaceuticals, Beijing Institute of Technology, 5 South Zhongguancun Street, Haidian District, Beijing 100081, China
- School of Life Science, Beijing Institute of Technology, 5 South Zhongguancun Street, Haidian District, Beijing 100081, China
| | - Zhao Li
- Institute of Engineering Medicine, School of Medical Technology, Beijing Institute of Technology, 5 South Zhongguancun Street, Haidian District, Beijing 100081, China
- Beijing Key Laboratory for Separation and Analysis in Biomedicine and Pharmaceuticals, Beijing Institute of Technology, 5 South Zhongguancun Street, Haidian District, Beijing 100081, China
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Dysregulation of Mir-193B and Mir-376A as a Biomarker of Prediabetes in Offspring of Gestational Diabetic Mice. Processes (Basel) 2022. [DOI: 10.3390/pr10122551] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022] Open
Abstract
Gestational diabetes mellitus (GDM) is a type of diabetes initiated during pregnancy and is characterized by maternal hyperglycemia that induces complications in mothers and children. In the current study, we used a GDM mouse model (through i.p. injection of a single dose of streptozocin, STZ, 60 mg/kg/bw) to investigate the biochemical and immunological changes in the blood and brain of diabetic mothers and their offspring relative to their appropriate controls. In addition, we estimated the expression levels of a set of microRNAs (miRNAs) to link between the dysregulation in the levels of miRNAs and the exposure to oxidative stress during embryonic development, as well as metabolic changes that occur after birth and during puberty in offspring (5-weeks-old). At the biochemical level, newborn pups appeared mostly to suffer from the same oxidative stress conditions of their mothers as shown by the significant increase in nitric oxide (NO) and malondialdehyde (MDA) in blood and brain of diabetic mothers and their pups. However, the 5-week-old offspring showed a significant increase in proinflammatory cytokines, IL-1β, IL-6, and TNF-α, and based on their blood glucose levels, could be considered as prediabetic (with glucose mean value of 165 mg/dl). In the meantime, the tested miRNAs, especially miR-15b, miR-146a, and miR-138 showed mostly similar expression levels in diabetic mothers and newborn pups. In this regard, miR-15a and -15b, miR-146a, and miR-138 are downregulated in diabetic mothers and their newborn pups relative to their appropriate controls. However, in offspring of diabetic mothers at puberty age, these miRNAs displayed different expression levels relative to mothers and control offspring. Interestingly, miR-193 and miR-763 expression levels were significantly lower in diabetic mothers but upregulated in their 5-week-old offspring, suggesting that miR-193 and miR-763 could be used as biomarkers to differentiate between prediabetes and diabetes.
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Navarro-Ruiz MC, Soler-Vázquez MC, Díaz-Ruiz A, Peinado JR, Nieto Calonge A, Sánchez-Ceinos J, Tercero-Alcázar C, López-Alcalá J, Rangel-Zuñiga OA, Membrives A, López-Miranda J, Malagón MM, Guzmán-Ruiz R. Influence of Protein Carbonylation on Human Adipose Tissue Dysfunction in Obesity and Insulin Resistance. Biomedicines 2022; 10:biomedicines10123032. [PMID: 36551793 PMCID: PMC9775537 DOI: 10.3390/biomedicines10123032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Revised: 10/28/2022] [Accepted: 11/14/2022] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND Obesity is characterized by adipose tissue dysregulation and predisposes individuals to insulin resistance and type 2 diabetes. At the molecular level, adipocyte dysfunction has been linked to obesity-triggered oxidative stress and protein carbonylation, considering protein carbonylation as a link between oxidative stress and metabolic dysfunction. The identification of specific carbonylated proteins in adipose tissue could provide novel biomarkers of oxidative damage related to metabolic status (i.e prediabetes). Thus, we aimed at characterizing the subcutaneous and omental human adipose tissue carbonylome in obesity-associated insulin resistance. METHODS 2D-PAGE was used to identify carbonylated proteins, and clinical correlations studies and molecular biology approaches including intracellular trafficking, reactive oxygen species assay, and iron content were performed using in vitro models of insulin resistance. RESULTS The carbonylome of human adipose tissue included common (serotransferrin, vimentin, actin, and annexin A2) and depot-specific (carbonic anhydrase and α-crystallin B in the subcutaneous depot; and α-1-antitrypsin and tubulin in the omental depot) differences that point out the complexity of oxidative stress at the metabolic level, highlighting changes in carbonylated transferrin expression. Posterior studies using in vitro prediabetic model evidence alteration in transferrin receptor translocation, linked to the prediabetic environment. Finally, ligand-receptor molecular docking studies showed a reduced affinity for carbonylated transferrin binding to its receptor compared to wild-type transferrin, emphasizing the role of transferrin carbonylation in the link between oxidative stress and metabolic dysfunction. CONCLUSIONS The adipose tissue carbonylome contributes to understanding the molecular mechanism driving adipocyte dysfunction and identifies possible adipose tissue carbonylated targets in obesity-associated insulin resistance.
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Affiliation(s)
- M. Carmen Navarro-Ruiz
- Department of Cell Biology, Physiology, and Immunology, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, 14014 Córdoba, Spain
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - M. Carmen Soler-Vázquez
- Department of Cell Biology, Physiology, and Immunology, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, 14014 Córdoba, Spain
| | - Alberto Díaz-Ruiz
- Nutritional Interventions Group, Precision Nutrition and Aging, Madrid Institute for Advanced Studies—IMDEA Food, CEI UAM+CSIC, 28049 Madrid, Spain
| | - Juan R. Peinado
- Oxidative Stress and Neurodegeneration Group, Regional Center for Biomedical Research, Department of Medical Sciences, Ciudad Real Medical School, University of Castilla-La Mancha, 13001 Ciudad Real, Spain
| | - Andrea Nieto Calonge
- Department of Cell Biology, Physiology, and Immunology, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, 14014 Córdoba, Spain
| | - Julia Sánchez-Ceinos
- Department of Cell Biology, Physiology, and Immunology, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, 14014 Córdoba, Spain
| | - Carmen Tercero-Alcázar
- Department of Cell Biology, Physiology, and Immunology, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, 14014 Córdoba, Spain
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Jaime López-Alcalá
- Department of Cell Biology, Physiology, and Immunology, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, 14014 Córdoba, Spain
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Oriol A. Rangel-Zuñiga
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, 28029 Madrid, Spain
- Lipids and Atherosclerosis Unit, IMIBIC, Reina Sofia University Hospital, University of Córdoba, 14004 Córdoba, Spain
| | - Antonio Membrives
- General and Digestive Surgery Clinical Management Unit, Obesity Section, IMIBIC, Reina Sofía University Hospital, 14004 Córdoba, Spain
| | - José López-Miranda
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, 28029 Madrid, Spain
- Lipids and Atherosclerosis Unit, IMIBIC, Reina Sofia University Hospital, University of Córdoba, 14004 Córdoba, Spain
| | - María M. Malagón
- Department of Cell Biology, Physiology, and Immunology, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, 14014 Córdoba, Spain
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, 28029 Madrid, Spain
- Correspondence: (M.M.M.); (R.G.-R.); Tel.: +34-957213778 (R.G.-R.)
| | - Rocío Guzmán-Ruiz
- Department of Cell Biology, Physiology, and Immunology, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, 14014 Córdoba, Spain
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, 28029 Madrid, Spain
- Correspondence: (M.M.M.); (R.G.-R.); Tel.: +34-957213778 (R.G.-R.)
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H19 and TUG1 lncRNAs as Novel Biomarkers for Irritable Bowel Syndrome in Diabetic Patients. Biomedicines 2022; 10:biomedicines10112978. [PMID: 36428545 PMCID: PMC9687602 DOI: 10.3390/biomedicines10112978] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Revised: 11/10/2022] [Accepted: 11/16/2022] [Indexed: 11/22/2022] Open
Abstract
Introduction: Irritable bowel syndrome (IBS) is a gastrointestinal disorder due to enteric nervous system impairment that produces different patterns of digestion. IBS is a common finding in diabetic patients. The functions of lncRNAs in IBS are still not clear and need to be further investigated. The aim of this study was to assess the diagnostic roles of lncRNA H19 and TUG1 for IBS associated with diabetes and to evaluate their association with clinical and laboratory findings. Subjects and Methods: Samples from 42 diabetic patients, 42 diabetic patients with IBS, and 42 healthy controls were obtained. The LncRNA H19 and TUG1 expressions were measured by quantitative real-time PCR. Results: The patients with IBS had significantly lower levels of lncRNA H19 and TUG1 expression than the healthy controls and diabetic-only patients (p < 0.001). LncRNA H19 and TUG1 can discriminate between diabetic-only patients and those with IBS (areas under the ROC curves of 0.95 and 0.722, respectively). The TUG1 expression levels were significantly different among types of IBS (IBS-D lower than IBS-M and IBS-C lower than IBS-M; p = 0.0165 and p = 0.043, respectively). H19 and TUG1 were downregulated in patients with poor glycemic control. lncRNA H19 and TUG1 expression in diabetic patients with IBS significantly negatively correlated with the IBS severity scoring system. Both lncRNAs’ expression significantly predicted the disease severity. LncRNA H19 expression can be an independent predictor for disease severity (adjusted odds ratio = 0.00001, 95% CI = 0−0.5, p = 0.045). Conclusions: Diabetic patients with IBS had significantly lower levels of lncRNA H19 and TUG1 expression than healthy controls and diabetic-only patients. LncRNA H19 had better diagnostic performance criteria for IBS. LncRNA H19 expression can be an independent predictor for IBS severity.
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Teng J, Yue L, Li B, Yang J, Yang C, Yang T, Zhi X, Liu X, Zhao Y, Zhang J. Synthesis of Cyclodextrin‐based temperature/enzyme‐responsive nanoparticles and application in antitumor drug delivery. J Mol Struct 2022. [DOI: 10.1016/j.molstruc.2022.134596] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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Safdar R, Thanabalan M. Developments in insulin delivery and potential of chitosan for controlled release application: A review. J Drug Deliv Sci Technol 2022. [DOI: 10.1016/j.jddst.2022.103873] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022]
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Al-Nemrawi NK, Darweesh RS, Al-shriem LA, Al-Qawasmi FS, Emran SO, Khafajah AS, Abu-Dalo MA. Polymeric Nanoparticles for Inhaled Vaccines. Polymers (Basel) 2022; 14:4450. [PMID: 36298030 PMCID: PMC9607145 DOI: 10.3390/polym14204450] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Revised: 10/04/2022] [Accepted: 10/07/2022] [Indexed: 11/07/2022] Open
Abstract
Many recent studies focus on the pulmonary delivery of vaccines as it is needle-free, safe, and effective. Inhaled vaccines enhance systemic and mucosal immunization but still faces many limitations that can be resolved using polymeric nanoparticles (PNPs). This review focuses on the use of properties of PNPs, specifically chitosan and PLGA to be used in the delivery of vaccines by inhalation. It also aims to highlight that PNPs have adjuvant properties by themselves that induce cellular and humeral immunogenicity. Further, different factors influence the behavior of PNP in vivo such as size, morphology, and charge are discussed. Finally, some of the primary challenges facing PNPs are reviewed including formulation instability, reproducibility, device-related factors, patient-related factors, and industrial-level scale-up. Herein, the most important variables of PNPs that shall be defined in any PNPs to be used for pulmonary delivery are defined. Further, this study focuses on the most popular polymers used for this purpose.
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Affiliation(s)
- Nusaiba K. Al-Nemrawi
- Department of Pharmaceutical Technology, Faculty of Pharmacy, Jordan University of Science and Technology, P.O. Box 3030, Irbid 22110, Jordan
| | - Ruba S. Darweesh
- Department of Pharmaceutical Technology, Faculty of Pharmacy, Jordan University of Science and Technology, P.O. Box 3030, Irbid 22110, Jordan
| | - Lubna A. Al-shriem
- Department of Pharmaceutical Technology, Faculty of Pharmacy, Jordan University of Science and Technology, P.O. Box 3030, Irbid 22110, Jordan
| | - Farah S. Al-Qawasmi
- Department of Pharmaceutical Technology, Faculty of Pharmacy, Jordan University of Science and Technology, P.O. Box 3030, Irbid 22110, Jordan
| | - Sereen O. Emran
- Department of Pharmaceutical Technology, Faculty of Pharmacy, Jordan University of Science and Technology, P.O. Box 3030, Irbid 22110, Jordan
| | - Areej S. Khafajah
- Department of Pharmaceutical Technology, Faculty of Pharmacy, Jordan University of Science and Technology, P.O. Box 3030, Irbid 22110, Jordan
| | - Muna A. Abu-Dalo
- Department of Chemistry, Faculty of Science and Art, Jordan University of Science and Technology, P.O. Box 3030, Irbid 22110, Jordan
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Galectin-1 in Obesity and Type 2 Diabetes. Metabolites 2022; 12:metabo12100930. [PMID: 36295832 PMCID: PMC9606923 DOI: 10.3390/metabo12100930] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 09/26/2022] [Accepted: 09/26/2022] [Indexed: 11/06/2022] Open
Abstract
Galectin-1 is a carbohydrate-binding protein expressed in many tissues. In recent years, increasing evidence has emerged for the role of galectin-1 in obesity, insulin resistance and type 2 diabetes. Galectin-1 has been highly conserved through evolution and is involved in key cellular functions such as tissue maturation and homeostasis. It has been shown that galectin-1 increases in obesity, both in the circulation and in the adipose tissue of human and animal models. Several proteomic studies have independently identified an increased galectin-1 expression in the adipose tissue in obesity and in insulin resistance. Large population-based cohorts have demonstrated associations for circulating galectin-1 and markers of insulin resistance and incident type 2 diabetes. Furthermore, galectin-1 is associated with key metabolic pathways including glucose and lipid metabolism, as well as insulin signalling and inflammation. Intervention studies in animal models alter animal weight and metabolic profile. Several studies have also linked galectin-1 to the progression of complications in diabetes, including kidney disease and retinopathy. Here, we review the current knowledge on the clinical potential of galectin-1 in obesity and type 2 diabetes.
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Martínez-López AL, Carvajal-Millan E, Canett-Romero R, Prakash S, Rascón-Chu A, López-Franco YL, Lizardi-Mendoza J, Micard V. Arabinoxylans-Based Oral Insulin Delivery System Targeting the Colon: Simulation in a Human Intestinal Microbial Ecosystem and Evaluation in Diabetic Rats. Pharmaceuticals (Basel) 2022; 15:ph15091062. [PMID: 36145283 PMCID: PMC9504777 DOI: 10.3390/ph15091062] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Revised: 08/12/2022] [Accepted: 08/24/2022] [Indexed: 11/16/2022] Open
Abstract
Arabinoxylans (AX) microcapsules loaded with insulin were prepared by enzymatic gelation of AX, using a triaxial electrospray method. The microcapsules presented a spherical shape, with an average size of 250 µm. The behavior of AX microcapsules was evaluated using a simulator of the human intestinal microbial ecosystem. AX microcapsules were mainly (70%) degraded in the ascending colon. The fermentation was completed in the descending colon, increasing the production of acetic, propionic, and butyric acids. In the three regions of the colon, the fermentation of AX microcapsules significantly increased populations of Bifidobacterium and Lactobacillus and decreased the population of Enterobacteriaceae. In addition, the results found in this in vitro model showed that the AX microcapsules could resist the simulated conditions of the upper gastrointestinal system and be a carrier for insulin delivery to the colon. The pharmacological activity of insulin-loaded AX microcapsules was evaluated after oral delivery in diabetic rats. AX microcapsules lowered the serum glucose levels in diabetic rats by 75%, with insulin doses of 25 and 50 IU/kg. The hypoglycemic effect and the insulin levels remained for more than 48 h. Oral relative bioavailability was 13 and 8.7% for the 25 and 50 IU/kg doses, respectively. These results indicate that AX microcapsules are a promising microbiota-activated system for oral insulin delivery in the colon.
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Affiliation(s)
- Ana L. Martínez-López
- Research Center for Food and Development, CIAD, A.C. Carretera a La Victoria Km. 0.6, Hermosillo 83304, Sonora, Mexico
- NANO-VAC Research Group, Department of Chemistry and Pharmaceutical Technology, University of Navarra, 31008 Pamplona, Spain
- Correspondence: (A.L.M.-L.); (E.C.-M.); Tel.: +52-662-2892400 (A.L.M.-L.); Fax: +52-662-2800421 (A.L.M.-L.)
| | - Elizabeth Carvajal-Millan
- Research Center for Food and Development, CIAD, A.C. Carretera a La Victoria Km. 0.6, Hermosillo 83304, Sonora, Mexico
- Correspondence: (A.L.M.-L.); (E.C.-M.); Tel.: +52-662-2892400 (A.L.M.-L.); Fax: +52-662-2800421 (A.L.M.-L.)
| | - Rafael Canett-Romero
- Departamento de Investigación y Posgrado en Alimentos, Universidad de Sonora, Rosales y Blvd. Luis D. Colosio, Hermosillo 83000, Sonora, Mexico
| | - Satya Prakash
- Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering, Faculty of Medicine, Artificial Cell and Organs Research Centre, McGill University, Montreal, QC H3A 0G4, Canada
| | - Agustín Rascón-Chu
- Research Center for Food and Development, CIAD, A.C. Carretera a La Victoria Km. 0.6, Hermosillo 83304, Sonora, Mexico
| | - Yolanda L. López-Franco
- Research Center for Food and Development, CIAD, A.C. Carretera a La Victoria Km. 0.6, Hermosillo 83304, Sonora, Mexico
| | - Jaime Lizardi-Mendoza
- Research Center for Food and Development, CIAD, A.C. Carretera a La Victoria Km. 0.6, Hermosillo 83304, Sonora, Mexico
| | - Valerie Micard
- Montpellier SupAgro-INRA-UM-CIRAD, JRU IATE, 2, Place Pierre Viala, CEDEX 01, 34060 Montpellier, France
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Katayama D, Nagano N, Shimizu S, Nakazaki K, Matsuda K, Tokunaga W, Fuwa K, Aoki R, Morioka I. A Non-Obese Hyperglycemic Mouse Model that Develops after Birth with Low Birthweight. Biomedicines 2022; 10:biomedicines10071642. [PMID: 35884949 PMCID: PMC9312481 DOI: 10.3390/biomedicines10071642] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 07/02/2022] [Accepted: 07/07/2022] [Indexed: 11/29/2022] Open
Abstract
The number of low birthweight (LBW) infants weighing below 2500 g has not decreased in Japan. This study aimed to develop an adult non-obese hyperglycemic mouse model born with LBW to study the pathogenesis. At 16.5 days of gestation, transient intrauterine ischemia (blocked blood flow in both uterine arteries for 15 min) was performed in a subgroup of pregnant mice (group I). Non-occluded dams were used as sham controls (group C). After birth, female pups in each group were weaned at 4 weeks of age and reared on the normal diet until 8 weeks of age (n = 7). Fasting blood glucose levels, serum immunoreactive insulin (IRI), and body composition were then measured. Metabolite analyses was performed on the liver tissues. Birthweight was significantly lower in group I compared with group C. Pups from group I remained underweight with low fat-free mass and showed hyperglycemia with high serum IRI and homeostasis model assessment of insulin resistance levels, indicating insulin resistance. Metabolite analyses showed significantly reduced adenosine triphosphate and nicotinamide adenine dinucleotide production and increased lactic acid in group I. The pathogenesis of our non-obese hyperglycemic mouse model may be due to increased myogenic insulin resistance based on mitochondrial dysfunction and reduced lean body mass.
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Rhea EM, Banks WA, Raber J. Insulin Resistance in Peripheral Tissues and the Brain: A Tale of Two Sites. Biomedicines 2022; 10:1582. [PMID: 35884888 PMCID: PMC9312939 DOI: 10.3390/biomedicines10071582] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Revised: 06/27/2022] [Accepted: 06/29/2022] [Indexed: 12/12/2022] Open
Abstract
The concept of insulin resistance has been around since a few decades after the discovery of insulin itself. To allude to the classic Charles Dicken's novel published 62 years before the discovery of insulin, in some ways, this is the best of times, as the concept of insulin resistance has expanded to include the brain, with the realization that insulin has a life beyond the regulation of glucose. In other ways, it is the worst of times as insulin resistance is implicated in devastating diseases, including diabetes mellitus, obesity, and Alzheimer's disease (AD) that affect the brain. Peripheral insulin resistance affects nearly a quarter of the United States population in adults over age 20. More recently, it has been implicated in AD, with the degree of brain insulin resistance correlating with cognitive decline. This has led to the investigation of brain or central nervous system (CNS) insulin resistance and the question of the relation between CNS and peripheral insulin resistance. While both may involve dysregulated insulin signaling, the two conditions are not identical and not always interlinked. In this review, we compare and contrast the similarities and differences between peripheral and CNS insulin resistance. We also discuss how an apolipoprotein involved in insulin signaling and related to AD, apolipoprotein E (apoE), has distinct pools in the periphery and CNS and can indirectly affect each system. As these systems are both separated but also linked via the blood-brain barrier (BBB), we discuss the role of the BBB in mediating some of the connections between insulin resistance in the brain and in the peripheral tissues.
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Affiliation(s)
- Elizabeth M. Rhea
- Department of Medicine, Division of Gerontology and Geriatric Medicine, University of Washington, Seattle, WA 98195, USA; (E.M.R.); (W.A.B.)
- Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA
| | - William A. Banks
- Department of Medicine, Division of Gerontology and Geriatric Medicine, University of Washington, Seattle, WA 98195, USA; (E.M.R.); (W.A.B.)
- Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA
| | - Jacob Raber
- Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, USA
- Departments of Neurology and Radiation Medicine, Division of Neuroscience, ONPRC, Oregon Health & Science University, Portland, OR 97239, USA
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