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Ai Z, Liu B, Chen J, Zeng X, Wang K, Tao C, Chen J, Yang L, Ding Q, Zhou M. Advances in nano drug delivery systems for enhanced efficacy of emodin in cancer therapy. Int J Pharm X 2025; 9:100314. [PMID: 39834843 PMCID: PMC11743866 DOI: 10.1016/j.ijpx.2024.100314] [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: 11/06/2024] [Revised: 12/13/2024] [Accepted: 12/15/2024] [Indexed: 01/05/2025] Open
Abstract
Cancer remains one of the leading causes of death worldwide, highlighting the urgent need for novel antitumor drugs. Natural products have long been a crucial source of anticancer agents. Among these, emodin (EMO), a multifunctional anthraquinone compound, exhibits significant anticancer effects but is hindered in clinical applications by challenges such as low solubility, rapid metabolism, poor bioavailability, and off-target toxicity. Nano drug delivery systems offer effective strategies to overcome these limitations by enhancing the solubility, stability, bioavailability, and targeting ability of EMO. While substantial progress has been made in developing EMO-loaded nanoformulations, a comprehensive review on this topic is still lacking. This paper aims to fill this gap by providing an overview of recent advancements in nanocarriers for EMO delivery and their anticancer applications. These carriers include liposomes, nanoparticles, polymeric micelles, nanogels, and others, with nanoparticle-based formulations being the most extensively explored. Nanoformulations encapsulating EMO have demonstrated promising therapeutic results against various cancers, particularly breast cancer, followed by liver and lung cancers. We systematically summarize the preparation methods, materials, and physicochemical properties of EMO-loaded nanopreparations, underscoring key findings on how nanotechnology improves the anticancer efficacy of EMO. This review provides valuable insights for researchers engaged in developing nano delivery systems for anticancer drugs.
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Affiliation(s)
- Zhenghao Ai
- Department of Pharmacy, The Affiliated Hospital, Southwest Medical University, Luzhou, China
| | - Bingyao Liu
- Department of Radiology, West China Hospital Sichuan University Jintang Hospital, Chengdu, China
| | - Junyan Chen
- Department of Cardiothoracic Surgery, Luzhou People's Hospital, Luzhou, China
| | - Xinhao Zeng
- Department of Pediatric Surgery, The Affiliated Hospital of Southwest Medical University, Sichuan Clinical Research Center for Birth Defects, Luzhou, China
| | - Ke Wang
- Department of Pharmacy, The Affiliated Hospital, Southwest Medical University, Luzhou, China
| | - Chao Tao
- Department of Pharmacy, The Affiliated Hospital, Southwest Medical University, Luzhou, China
| | - Jing Chen
- Department of Clinical Pharmacy, The Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, China
| | - Liuxuan Yang
- Department of Pharmacy, The Affiliated Hospital, Southwest Medical University, Luzhou, China
| | - Qian Ding
- Department of Clinical Pharmacy, The Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, China
| | - Meiling Zhou
- Department of Pharmacy, The Affiliated Hospital, Southwest Medical University, Luzhou, China
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Zhang C, Wang Y, Cui X, Zhang Q, Cong H, Liu J, Ren J, Tang J. Emodin nanocrystals enhanced mucus penetration and ameliorated bleomycin-induced pulmonary fibrosis by pulmonary delivery. J Drug Target 2025:1-11. [PMID: 40266897 DOI: 10.1080/1061186x.2025.2497369] [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: 03/06/2025] [Revised: 04/08/2025] [Accepted: 04/20/2025] [Indexed: 04/25/2025]
Abstract
Pulmonary fibrosis (PF) is a progressive interstitial disease characterised by extracellular matrix deposition and destruction of lung tissue structure. Emodin (Emo) is a natural active compound with anti-inflammatory and antioxidant properties. The initiation of PF is prevented by reducing oxidative stress-induced damage to alveolar epithelial cells." to meet the word count requirement. However, Emo is featured low water solubility, a rapid metabolic rate and low oral bioavailability, which limit its application in the treatment of PF. Therefore, this study formulated emodin as nanocrystals (Emo-NCs) and delivered Emo directly to the lesion site via pulmonary delivery to enhance drug efficacy. The Emo-NCs exhibited a square crystal structure with particle sizes suitable for pulmonary absorption and an appropriate polydispersity index. They released 99.38% over 48 h and significantly improved permeability efficiency in simulated pulmonary mucus. The ability of Emo-NCs to inhibit abnormal fibroblast proliferation and oxidative damage was significantly enhanced compared with Emo. In contrast to the BLM group, the inflammatory cells in the lung tissue sections of the Emo-NCs group were significantly reduced, the alveolar structure was largely restored, and no evident collagen fibre deposition was observed. In summary, Emo-NCs could serve as a viable delivery system for site-specific treatment of PF.
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Affiliation(s)
- Chenghao Zhang
- School of Pharmacy, Harbin Medical University, Harbin, China
| | - Yihua Wang
- School of Pharmacy, Harbin Medical University, Harbin, China
| | - Xinran Cui
- School of Pharmacy, Harbin Medical University, Harbin, China
- Liaoning Cancer Hospital &Institute, Shenyang, China
| | - Qing Zhang
- School of Pharmacy, Harbin Medical University, Harbin, China
| | - Huijing Cong
- School of Pharmacy, Harbin Medical University, Harbin, China
| | - Jiaxin Liu
- School of Pharmacy, Harbin Medical University, Harbin, China
| | - Jinmei Ren
- Qingpu Branch of Zhongshan Hospital, Affiliated to Fudan University, Shanghai, China
| | - Jingling Tang
- School of Pharmacy, Harbin Medical University, Harbin, China
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Bhadouria VS, Verma S, Agarwal C, Sharma DS. From Patents to Progress: Unraveling Gout's Journey Through Clinical Trials and Advancements. Rev Recent Clin Trials 2025; 20:96-112. [PMID: 39385411 DOI: 10.2174/0115748871308473240926044126] [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: 02/26/2024] [Revised: 07/19/2024] [Accepted: 08/08/2024] [Indexed: 10/12/2024]
Abstract
Gout, an inflammatory arthritis form, is renowned for its historical association with affluence. This review delves into its pathophysiology, exploring hyperuricemia, urate crystal formation, and the ensuing inflammatory response. The epidemiology of gout is examined, focusing on its rising prevalence and impact on public health. In this study, progress in gout management is discussed, involving pharmacological interventions, dietary changes, and emerging therapies. Genetic predisposition and triggers like alcohol, temperature, and diet are highlighted in this study. Prevention strategies, including serum urate-lowering therapy and lifestyle modifications, aim to reduce recurrent flares and complications. The inflammatory response in acute gout attacks is elucidated, involving immune cells, cytokines, and the NLRP3 inflammasome. Chronic gout manifestations, such as gouty tophus formation, are explored for their destructive impact on surrounding tissues. Recent advancements in gout treatment, including nanotherapies and novel compounds, are discussed, along with promising urate-lowering drugs. Cutting-edge research on zinc ferrite nanoparticles, dimethyl fumarate, and myricetin/nobiletin hybrids addresses oxidative stress and inflammation in gout. Additionally, the potential therapeutic role of methanolic leaf extract of Euphorbia milii and tip-loaded CLC-Soluplus® MAPs is explored as natural and transdermal alternatives for gout management. The review also covers the development status of new urate-lowering drugs, providing insights into promising candidates and their mechanisms. Patents on gout and recent diagnostic advancements using techniques like laser confocal micro Raman spectrometer, FTIR, and THz-TDS offer a more accurate approach for gout stone analysis, enabling early detection and targeted treatment.
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Affiliation(s)
- Vikash Singh Bhadouria
- Department of Pharmaceutics, Noida Institute of Engineering and Technology (Pharmacy Institute), Greater Noida, 201306, India
| | - Sushma Verma
- Department of Pharmaceutics, Noida Institute of Engineering and Technology (Pharmacy Institute), Greater Noida, 201306, India
| | - Chhaya Agarwal
- Department of Biotechnology, Noida Institute of Engineering and Technology, Greater Noida, 201306, India
| | - Deep Shikha Sharma
- Department of Pharmaceutics, Lovely Professional University, Phagwara, Punjab, 144001, India
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Shan X, Lv S, Cheng H, Zhou L, Gao Y, Xing C, Li D, Tao W, Zhang C. Evaluation of 3-O-β-D-galactosylated resveratrol-loaded polydopamine nanoparticles for hepatocellular carcinoma treatment. Eur J Pharm Biopharm 2024; 203:114454. [PMID: 39142541 DOI: 10.1016/j.ejpb.2024.114454] [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: 04/10/2024] [Revised: 07/21/2024] [Accepted: 08/12/2024] [Indexed: 08/16/2024]
Abstract
In our previous studies, 3-O-β-D-galactosylated resveratrol (Gal-Res) was synthesized by structural modification and then 3-O-β-D-galactosylated resveratrol polydopamine nanoparticles (Gal-Res NPs) were successfully prepared to improve the bioavailability and liver distribution of Res. However, the pharmacodynamic efficacy and specific mechanism of Gal-Res NPs on hepatocellular carcinoma remain unclear. Herein, liver cancer model mice were successfully constructed by xenograft tumor modeling. Gal-Res NPs (34.2 mg/kg) significantly inhibited tumor growth of the liver cancer model mice with no significant effect on their body weight and no obvious toxic effect on major organs. Additionally, in vitro cellular uptake assay showed that Gal-Res NPs (37.5 μmol/L) increased the uptake of Gal-Res by Hepatocellular carcinoma (HepG2) cells, and significantly inhibited the cell migration and invasion. The experimental results of Hoechst 33342/propyl iodide (PI) double staining and flow cytometry both revealed that Gal-Res NPs could remarkably promote cell apoptosis. Moreover, the Western blot results revealed that Gal-Res NPs significantly regulated the Bcl-2/Bax and AKT/GSK3β/β-catenin signaling pathways. Taken together, the in vitro/in vivo results demonstrated that Gal-Res NPs significantly improved the antitumor efficiency of Gal-Res, which is a potential antitumor drug delivery system.
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Affiliation(s)
- Xiaoxiao Shan
- Center for Xin'an Medicine and Modernization of Traditional Chinese Medicine of IHM, Grand Health Research Institute of Hefei Comprehensive National Science Center, School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China; Anhui Province Key Laboratory of Pharmaceutical Preparation Technology and Application, Anhui University of Chinese Medicine, Hefei 230012, China; Engineering Technology Research Center of Modernized Pharmaceutics, Anhui Education Department (AUCM), Hefei 230012, Anhui, China
| | - Shujie Lv
- Center for Xin'an Medicine and Modernization of Traditional Chinese Medicine of IHM, Grand Health Research Institute of Hefei Comprehensive National Science Center, School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China; Anhui Province Key Laboratory of Pharmaceutical Preparation Technology and Application, Anhui University of Chinese Medicine, Hefei 230012, China; Engineering Technology Research Center of Modernized Pharmaceutics, Anhui Education Department (AUCM), Hefei 230012, Anhui, China
| | - Hongyan Cheng
- Center for Xin'an Medicine and Modernization of Traditional Chinese Medicine of IHM, Grand Health Research Institute of Hefei Comprehensive National Science Center, School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China; Anhui Province Key Laboratory of Pharmaceutical Preparation Technology and Application, Anhui University of Chinese Medicine, Hefei 230012, China; Engineering Technology Research Center of Modernized Pharmaceutics, Anhui Education Department (AUCM), Hefei 230012, Anhui, China
| | - Lele Zhou
- Center for Xin'an Medicine and Modernization of Traditional Chinese Medicine of IHM, Grand Health Research Institute of Hefei Comprehensive National Science Center, School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China; Anhui Province Key Laboratory of Pharmaceutical Preparation Technology and Application, Anhui University of Chinese Medicine, Hefei 230012, China; Engineering Technology Research Center of Modernized Pharmaceutics, Anhui Education Department (AUCM), Hefei 230012, Anhui, China
| | - Yu Gao
- Center for Xin'an Medicine and Modernization of Traditional Chinese Medicine of IHM, Grand Health Research Institute of Hefei Comprehensive National Science Center, School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China; Anhui Province Key Laboratory of Pharmaceutical Preparation Technology and Application, Anhui University of Chinese Medicine, Hefei 230012, China; Engineering Technology Research Center of Modernized Pharmaceutics, Anhui Education Department (AUCM), Hefei 230012, Anhui, China
| | - Chengjie Xing
- Center for Xin'an Medicine and Modernization of Traditional Chinese Medicine of IHM, Grand Health Research Institute of Hefei Comprehensive National Science Center, School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China; Anhui Province Key Laboratory of Pharmaceutical Preparation Technology and Application, Anhui University of Chinese Medicine, Hefei 230012, China; Engineering Technology Research Center of Modernized Pharmaceutics, Anhui Education Department (AUCM), Hefei 230012, Anhui, China
| | - Dawei Li
- Center for Xin'an Medicine and Modernization of Traditional Chinese Medicine of IHM, Grand Health Research Institute of Hefei Comprehensive National Science Center, School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China; Anhui Province Key Laboratory of Pharmaceutical Preparation Technology and Application, Anhui University of Chinese Medicine, Hefei 230012, China; Engineering Technology Research Center of Modernized Pharmaceutics, Anhui Education Department (AUCM), Hefei 230012, Anhui, China
| | - Wenwen Tao
- Center for Xin'an Medicine and Modernization of Traditional Chinese Medicine of IHM, Grand Health Research Institute of Hefei Comprehensive National Science Center, School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China; Anhui Province Key Laboratory of Pharmaceutical Preparation Technology and Application, Anhui University of Chinese Medicine, Hefei 230012, China; Engineering Technology Research Center of Modernized Pharmaceutics, Anhui Education Department (AUCM), Hefei 230012, Anhui, China
| | - Caiyun Zhang
- Center for Xin'an Medicine and Modernization of Traditional Chinese Medicine of IHM, Grand Health Research Institute of Hefei Comprehensive National Science Center, School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China; Anhui Province Key Laboratory of Pharmaceutical Preparation Technology and Application, Anhui University of Chinese Medicine, Hefei 230012, China; Engineering Technology Research Center of Modernized Pharmaceutics, Anhui Education Department (AUCM), Hefei 230012, Anhui, China.
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Song H, Zhang J, Lou N, Jiang X, Cui Y, Liu J, Hu F, Jiao J, Pan C, Liu J, Wang Z, Shang D. Emodin nanocapsules inhibit acute pancreatitis by regulating lipid metabolic reprogramming in macrophage polarization. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 130:155763. [PMID: 38820661 DOI: 10.1016/j.phymed.2024.155763] [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: 02/24/2024] [Revised: 05/06/2024] [Accepted: 05/18/2024] [Indexed: 06/02/2024]
Abstract
BACKGROUND Emodin is a chemical compound found in traditional Chinese herbs. It possesses anti-inflammatory and many other pharmacological effects. Our previous study showed that emodin significantly alleviates the inflammation effect of severe acute pancreatitis (SAP). However, its poor solubility, high toxicity and limited pancreas retention time hinder its clinical application. PURPOSE We aimed to prepare emodin nanocapsules with improved bioavailability to achieve the controlled release of emodin by targeting macrophages. Further, the mechanism of mannose-conjugated chitosan-coated lipid nanocapsules loaded with emodin (M-CS-E-LNC) in the treatment of SAP was explored. METHODS M-CS-E-LNC were prepared by the phase inversion method with slight modification. The expression of inflammation mediators and the anti-inflammation efficacy of M-CS-E-LNC were examined by ELISA, IHC and IF in macrophage cells and LPS-induced SAP mice. IVIS spectrum imaging and HPLC were applied to explore the controlled release of M-CS-E-LNC in the pancreas. LC-MS/MS was performed for lipidomics analysis of macrophages. Moreover, a vector-based short hairpin RNA (shRNA) method was used to silence CTP1 gene expression in macrophage cells. RESULTS The levels of inflammatory mediators in macrophages were markedly decreased after treatment with M-CS-E-LNC. The same anti-inflammation effects were detected in SAP mouse through the analysis of serum levels of amylase, TNF-α and IL-6. Importantly, M-CS-E-LNC allowed the emodin to selectively accumulate at pancreas and gastrointestinal tissues, thus exhibiting a targeted release. Mechanistically, the M-CS-E-LNC treatment group showed up-regulated expression of the carnitine palmitoyltransferase 1 (CPT1) protein which promoted intracellular long-chain fatty acid transport, thereby promoting the M2 phenotype polarization of macrophages. CONCLUSION M-CS-E-LNC exhibited significantly improved bioavailability and water solubility, which translated to greater therapeutic effects on macrophage polarization. Our findings also demonstrate, for the first time, that CPT1 may be a new therapeutic target for SAP treatment.
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Affiliation(s)
- Huiyi Song
- Clinical Laboratory of Integrative Medicine, First Hospital affiliated to Dalian Medical University, Dalian, Liaoning, PR China
| | - Jianbin Zhang
- College of Pharmacy, Dalian Medical University, Dalian, Liaoning, PR China
| | - Ni Lou
- Clinical Laboratory of Integrative Medicine, First Hospital affiliated to Dalian Medical University, Dalian, Liaoning, PR China
| | - Xinyue Jiang
- Clinical Laboratory of Integrative Medicine, First Hospital affiliated to Dalian Medical University, Dalian, Liaoning, PR China
| | - Yuying Cui
- Clinical Laboratory of Integrative Medicine, First Hospital affiliated to Dalian Medical University, Dalian, Liaoning, PR China
| | - Jinming Liu
- The Third Department of General Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, PR China
| | - Fenglin Hu
- Clinical Laboratory of Integrative Medicine, First Hospital affiliated to Dalian Medical University, Dalian, Liaoning, PR China
| | - Juying Jiao
- Clinical Laboratory of Integrative Medicine, First Hospital affiliated to Dalian Medical University, Dalian, Liaoning, PR China
| | - Chen Pan
- Clinical Laboratory of Integrative Medicine, First Hospital affiliated to Dalian Medical University, Dalian, Liaoning, PR China
| | - Jianjun Liu
- Clinical Laboratory of Integrative Medicine, First Hospital affiliated to Dalian Medical University, Dalian, Liaoning, PR China
| | - Zhizhou Wang
- Clinical Laboratory of Integrative Medicine, First Hospital affiliated to Dalian Medical University, Dalian, Liaoning, PR China
| | - Dong Shang
- Clinical Laboratory of Integrative Medicine, First Hospital affiliated to Dalian Medical University, Dalian, Liaoning, PR China; The Third Department of General Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, PR China.
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Yehia RM, Lamie C, Attia DA. Microsponges-mediated targeted topical delivery of rosemary oil for hair growth promotion: optimization and in-vivo studies. Pharm Dev Technol 2024; 29:604-617. [PMID: 38958230 DOI: 10.1080/10837450.2024.2372572] [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: 03/30/2024] [Revised: 06/09/2024] [Accepted: 06/22/2024] [Indexed: 07/04/2024]
Abstract
Individuals experiencing hair loss, irrespective of gender, confront significant psychological challenges. This study explores the untapped potential of rosemary oil (ROS) to stimulate hair growth, addressing its limited permeability. The focus is on innovating ROS-loaded microsponges (MS) for enhanced topical application. Utilizing Box-Behnken design (33), the study optimizes ROS-MS compositions by varying solvent volume, polymer mix, and drug concentration. The optimized ROS-MS formulation exhibits noteworthy attributes: a 94% ± 0.04 production yield, 99.6% ± 0.5 encapsulation efficiency, and 96.4% ± 1.6 cumulative ROS release within 24 h. These microsponges exhibit uniformity with a particle size of 14.1 µm ± 4.5. The OPT-ROSMS-gel showcases favorable characteristics in appearance, spreadability, pH, drug content, and extrudability. Ex-vivo skin deposition tests highlight heightened permeability of OPT-ROSMS-gel compared to pure ROS-gel, resulting in three-fold increased follicular retention. In-vivo studies underscore the superior efficacy of OPT-ROSMS-gel, revealing enhanced hair development in length, thickness, and bulb diameter, surpassing ROS-gel and minoxidil by approximately 1.2 and 1.5 times, respectively, along with nearly two-fold increase in β-catenin levels. In conclusion, microsponges emerge as a promising ROS delivery method, effectively addressing hair loss. This research advances hair loss treatments and underscores the significance of this innovative paradigm in fostering hair growth.
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Affiliation(s)
- Rania M Yehia
- Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, The British University in Egypt (BUE), Cairo, Egypt
| | - Caroline Lamie
- Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, The British University in Egypt (BUE), Cairo, Egypt
| | - Dalia A Attia
- Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, The British University in Egypt (BUE), Cairo, Egypt
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Mehrdadi S. Lipid-Based Nanoparticles as Oral Drug Delivery Systems: Overcoming Poor Gastrointestinal Absorption and Enhancing Bioavailability of Peptide and Protein Therapeutics. Adv Pharm Bull 2024; 14:48-66. [PMID: 38585451 PMCID: PMC10997935 DOI: 10.34172/apb.2024.016] [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: 11/07/2022] [Revised: 08/09/2023] [Accepted: 10/08/2023] [Indexed: 04/09/2024] Open
Abstract
Delivery and formulation of oral peptide and protein therapeutics have always been a challenge for the pharmaceutical industry. The oral bioavailability of peptide and protein therapeutics mainly relies on their gastrointestinal solubility and permeability which are affected by their poor membrane penetration, high molecular weight and proteolytic (chemical and enzymatic) degradation resulting in limited delivery and therapeutic efficacy. The present review article highlights the challenges and limitations of oral delivery of peptide and protein therapeutics focusing on the application, potential and importance of solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) as lipid-based drug delivery systems (LBDDSs) and their advantages and drawbacks. LBDDSs, due to their lipid-based matrix can encapsulate both lipophilic and hydrophilic drugs, and by reducing the first-pass effect and avoiding proteolytic degradation offer improved drug stability, dissolution rate, absorption, bioavailability and controlled drug release. Furthermore, their small size, high surface area and surface modification increase their mucosal adhesion, tissue-targeted distribution, physiological function and half-life. Properties such as simple preparation, high-scale manufacturing, biodegradability, biocompatibility, prolonged half-life, lower toxicity, lower adverse effects, lipid-based structure, higher drug encapsulation rate and various drug release profile compared to other similar carrier systems makes LBDDSs a promising drug delivery system (DDS). Nevertheless, undesired physicochemical features of peptide and protein drug development and discovery such as plasma stability, membrane permeability and circulation half-life remain a serious challenge which should be addressed in future.
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Affiliation(s)
- Soheil Mehrdadi
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padua, Italy
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Saha P, Ahmad F. Neuroprotective, Anti-Inflammatory and Antifibrillogenic Offerings by Emodin against Alzheimer's Dementia: A Systematic Review. ACS OMEGA 2024; 9:7296-7309. [PMID: 38405501 PMCID: PMC10882671 DOI: 10.1021/acsomega.3c07178] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/21/2023] [Revised: 12/07/2023] [Accepted: 12/11/2023] [Indexed: 02/27/2024]
Abstract
Background: Alzheimer's disease (AD) is among the major causes of dementia in the elderly and exerts tremendous clinical, psychological and socio-economic constraints. Currently, there are no effective disease-modifying/retarding anti-AD agents. Emodin is a bioactive phytochemical with potent multimodal anti-inflammatory, antioxidant, and antifibrillogenic properties. In particular, emodin may result in significant repression of the pathogenic mechanisms underlying AD. The purpose of this review is to accumulate and summarize all the primary research data evaluating the therapeutic actions of emodin in AD pathogenesis. Methodology: The search, selection, and retrieval of pertinent primary research articles were systematically performed using a methodically designed approach. A variety of keyword combinations were employed on online scholarly web-databases. Strict preset inclusion and exclusion criteria were used to select the retrieved studies. Data from the individual studies were summarized and compiled into different sections, based upon their findings. Results: Cellular and animal research indicates that emodin exerts robust multimodal neuroprotection in AD. While emodin effectively prevents tau and amyloid-beta (Aβ) oligomerization, it also mitigates their neurotoxicity by attenuating neuroinflammatory, oxidative, and bioenergetic defects. Evidences for emodin-mediated enhancements in memory, learning, and cognition were also found in the literature. Conclusion: Emodin is a potential anti-AD dietary supplement; however, further studies are warrantied to thoroughly understand its target players and mechanisms. Moreover, human clinical data on emodin-mediated amelioration of AD phenotype is largely lacking, and must be addressed in the future. Lastly, the safety of exogenously supplemented emodin must be thoroughly evaluated.
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Affiliation(s)
- Priyanka Saha
- Department of Biotechnology, School of Bio Sciences and Technology (SBST), Vellore Institute of Technology, Vellore 632014, India
| | - Faraz Ahmad
- Department of Biotechnology, School of Bio Sciences and Technology (SBST), Vellore Institute of Technology, Vellore 632014, India
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Nguyen HT, Le AT, Nguyen TT, Huy TQ, Nguyen TTT. The role of chitosan in enhancing the solubility and antibacterial activity of emodin against drug-resistant bacteria. JOURNAL OF BIOMATERIALS SCIENCE. POLYMER EDITION 2024; 35:109-125. [PMID: 37843984 DOI: 10.1080/09205063.2023.2268964] [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: 12/23/2022] [Accepted: 10/02/2023] [Indexed: 10/18/2023]
Abstract
Similar to most anthraquinone compounds, the pharmacological properties of emodin are limited because of its low water solubility. In this study, the formulation of chitosan and emodin (EMD/CS) was prepared by a bottom-up method with precipitation and sonication steps in order to enhance the solubility of emodin. Thanks to the interactions of oxygen-and nitrogen-containing groups in chitosan with emodin molecules, the solubility of emodin in the formulation was remarkably increased to 0.5 mg/mL. The EMD/CS particles were well dispersed and distributed in a range of sub-micrometer with an average particle size of 342 nm. The EMD/CS formulation exhibited synergic antibacterial activity of emodin and chitosan, against drug-resistant bacterial strains, namely Methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli O157:H7 (E. coli O157:H7). When the compositions of emodin and chitosan increased, the antibacterial effectiveness of the EMD/CS formulation increased. The EMD/CS formulation with compositions of 0.5 mg/mL of emodin and 9.0 mg/mL of chitosan could significantly inhibit the proliferation of E. coli O157:H7. Meanwhile, the EMD/CS formulation with a lower concentration of emodin (0.4 mg/mL) and chitosan (7.2 mg/mL) could cause an extermination effect on MRSA. The enhanced solubility of EMD/CS formulation suggests that this formulation can be a potential candidate for the treatment of infectious diseases caused by drug-resistant bacterial pathogens.
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Affiliation(s)
- Hue Thi Nguyen
- Phenikaa University Nano Institute (PHENA), Phenikaa University, Hanoi, Vietnam
| | - Anh-Tuan Le
- Phenikaa University Nano Institute (PHENA), Phenikaa University, Hanoi, Vietnam
| | | | - Tran Quang Huy
- Phenikaa University Nano Institute (PHENA), Phenikaa University, Hanoi, Vietnam
- Faculty of Biomedical Sciences, Phenikaa University, Hanoi, Vietnam
| | - Thuy Thi Thu Nguyen
- Phenikaa University Nano Institute (PHENA), Phenikaa University, Hanoi, Vietnam
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10
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Okon E, Gaweł-Bęben K, Jarzab A, Koch W, Kukula-Koch W, Wawruszak A. Therapeutic Potential of 1,8-Dihydroanthraquinone Derivatives for Breast Cancer. Int J Mol Sci 2023; 24:15789. [PMID: 37958772 PMCID: PMC10648492 DOI: 10.3390/ijms242115789] [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: 10/09/2023] [Revised: 10/26/2023] [Accepted: 10/28/2023] [Indexed: 11/15/2023] Open
Abstract
Breast cancer (BC) is the most common malignancy among women worldwide. In recent years, significant progress has been made in BC therapy. However, serious side effects resulting from the use of standard chemotherapeutic drugs, as well as the phenomenon of multidrug resistance (MDR), limit the effectiveness of approved therapies. Advanced research in the BC area is necessary to create more effective and safer forms of therapy to improve the outlook for individuals diagnosed with this aggressive neoplasm. For decades, plants and natural products with anticancer properties have been successfully utilized in treating various medical conditions. Anthraquinone derivatives are tricyclic secondary metabolites of natural origin that have been identified in plants, lichens, and fungi. They represent a few botanical families, e.g., Rhamnaceae, Rubiaceae, Fabaceae, Polygonaceae, and others. The review comprehensively covers and analyzes the most recent advances in the anticancer activity of 1,8-dihydroanthraquinone derivatives (emodin, aloe-emodin, hypericin, chrysophanol, rhein, and physcion) applied both individually, or in combination with other chemotherapeutic agents, in in vitro and in vivo BC models. The application of nanoparticles for in vitro and in vivo evidence in the context of 1,8-dihydroanthraquinone derivatives was also described.
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Affiliation(s)
- Estera Okon
- Department of Biochemistry and Molecular Biology, Medical University of Lublin, 20-093 Lublin, Poland; (E.O.); (A.J.)
| | - Katarzyna Gaweł-Bęben
- Department of Cosmetology, University of Information Technology and Management in Rzeszów, 2 Sucharskiego, 35-225 Rzeszów, Poland;
| | - Agata Jarzab
- Department of Biochemistry and Molecular Biology, Medical University of Lublin, 20-093 Lublin, Poland; (E.O.); (A.J.)
| | - Wojciech Koch
- Department of Food and Nutrition, Medical University of Lublin, 4a Chodzki Str., 20-093 Lublin, Poland;
| | - Wirginia Kukula-Koch
- Department of Pharmacognosy with Medical Plants Garden, Medical University of Lublin, 1 Chodzki Str., 20-093 Lublin, Poland
| | - Anna Wawruszak
- Department of Biochemistry and Molecular Biology, Medical University of Lublin, 20-093 Lublin, Poland; (E.O.); (A.J.)
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11
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Ashfaq R, Rasul A, Asghar S, Kovács A, Berkó S, Budai-Szűcs M. Lipid Nanoparticles: An Effective Tool to Improve the Bioavailability of Nutraceuticals. Int J Mol Sci 2023; 24:15764. [PMID: 37958750 PMCID: PMC10648376 DOI: 10.3390/ijms242115764] [Citation(s) in RCA: 38] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2023] [Revised: 10/26/2023] [Accepted: 10/28/2023] [Indexed: 11/15/2023] Open
Abstract
Nano-range bioactive colloidal carrier systems are envisaged to overcome the challenges associated with treatments of numerous diseases. Lipid nanoparticles (LNPs), one of the extensively investigated drug delivery systems, not only improve pharmacokinetic parameters, transportation, and chemical stability of encapsulated compounds but also provide efficient targeting and reduce the risk of toxicity. Over the last decades, nature-derived polyphenols, vitamins, antioxidants, dietary supplements, and herbs have received more attention due to their remarkable biological and pharmacological health and medical benefits. However, their poor aqueous solubility, compromised stability, insufficient absorption, and accelerated elimination impede research in the nutraceutical sector. Owing to the possibilities offered by various LNPs, their ability to accommodate both hydrophilic and hydrophobic molecules and the availability of various preparation methods suitable for sensitive molecules, loading natural fragile molecules into LNPs offers a promising solution. The primary objective of this work is to explore the synergy between nature and nanotechnology, encompassing a wide range of research aimed at encapsulating natural therapeutic molecules within LNPs.
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Affiliation(s)
- Rabia Ashfaq
- Institute of Pharmaceutical Technology and Regulatory Affairs, Faculty of Pharmacy, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary; (R.A.)
| | - Akhtar Rasul
- Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad 38000, Pakistan; (A.R.); (S.A.)
| | - Sajid Asghar
- Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad 38000, Pakistan; (A.R.); (S.A.)
| | - Anita Kovács
- Institute of Pharmaceutical Technology and Regulatory Affairs, Faculty of Pharmacy, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary; (R.A.)
| | - Szilvia Berkó
- Institute of Pharmaceutical Technology and Regulatory Affairs, Faculty of Pharmacy, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary; (R.A.)
| | - Mária Budai-Szűcs
- Institute of Pharmaceutical Technology and Regulatory Affairs, Faculty of Pharmacy, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary; (R.A.)
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12
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Adedokun KA, Imodoye SO, Yahaya ZS, Oyeyemi IT, Bello IO, Adeyemo‐Imodoye MT, Sanusi MA, Kamorudeen RT. Nanodelivery of Polyphenols as Nutraceuticals in Anticancer Interventions. POLYPHENOLS 2023:188-224. [DOI: 10.1002/9781394188864.ch10] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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13
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Mahmoud KY, Elhesaisy NA, Rashed AR, Mikhael ES, Fadl MI, Elsadek MS, Mohamed MA, Mostafa MA, Hassan MA, Halema OM, Elnemer YH, Swidan SA. Exploring the potential of intranasally administered naturally occurring quercetin loaded into polymeric nanocapsules as a novel platform for the treatment of anxiety. Sci Rep 2023; 13:510. [PMID: 36627363 PMCID: PMC9831377 DOI: 10.1038/s41598-023-27665-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Accepted: 01/05/2023] [Indexed: 01/12/2023] Open
Abstract
Anxiety is one of the most prevalent forms of psychopathology that affects millions worldwide. It gained more importance under the pandemic status that resulted in higher anxiety prevalence. Anxiolytic drugs such as benzodiazepines have an unfavorable risk/benefit ratio resulting in a shift toward active ingredients with better safety profile such as the naturally occurring quercetin (QRC). The delivery of QRC is hampered by its low water solubility and low bioavailability. The potential to enhance QRC delivery to the brain utilizing polymeric nanocapsules administered intranasally is investigated in the current study. Polymeric nanocapsules were prepared utilizing the nanoprecipitation technique. The best formula displayed a particle size of 227.8 ± 11.9 nm, polydispersity index of 0.466 ± 0.023, zeta potential of - 17.5 ± 0.01 mV, and encapsulation efficiency % of 92.5 ± 1.9%. In vitro release of QRC loaded polymeric nanocapsules exhibited a biphasic release with an initial burst release followed by a sustained release pattern. Behavioral testing demonstrated the superiority of QRC loaded polymeric nanocapsules administered intranasally compared to QRC dispersion administered both orally and intranasally. The prepared QRC loaded polymeric nanocapsules also demonstrated good safety profile with high tolerability.
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Affiliation(s)
- Khaled Y. Mahmoud
- grid.440862.c0000 0004 0377 5514Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, 11837 Cairo Egypt
| | - Nahla A. Elhesaisy
- grid.440862.c0000 0004 0377 5514Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, 11837 Cairo Egypt
| | - Abdelrahman R. Rashed
- grid.440862.c0000 0004 0377 5514Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, 11837 Cairo Egypt
| | - Ebram S. Mikhael
- grid.440862.c0000 0004 0377 5514Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, 11837 Cairo Egypt
| | - Mahmoud I. Fadl
- grid.440862.c0000 0004 0377 5514Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, 11837 Cairo Egypt
| | - Mahmoud S. Elsadek
- grid.440862.c0000 0004 0377 5514Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, 11837 Cairo Egypt
| | - Merna A. Mohamed
- grid.440862.c0000 0004 0377 5514Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, 11837 Cairo Egypt
| | - Merna A. Mostafa
- grid.440862.c0000 0004 0377 5514Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, 11837 Cairo Egypt
| | - Mohamed A. Hassan
- grid.440862.c0000 0004 0377 5514Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, 11837 Cairo Egypt
| | - Omar M. Halema
- grid.440862.c0000 0004 0377 5514Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, 11837 Cairo Egypt
| | - Youssef H. Elnemer
- grid.440862.c0000 0004 0377 5514Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, 11837 Cairo Egypt
| | - Shady A. Swidan
- grid.440862.c0000 0004 0377 5514Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, 11837 Cairo Egypt
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14
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Jindal M, Kaur M, Nagpal M, Singh M, Aggarwal G, Dhingra GA. Skin Cancer Management: Current Scenario And Future Perspectives. Curr Drug Saf 2023; 18:143-158. [PMID: 35422227 DOI: 10.2174/1574886317666220413113959] [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: 10/13/2021] [Revised: 12/04/2021] [Accepted: 01/16/2022] [Indexed: 11/22/2022]
Abstract
Skin cancer is a life-threatening disease and has caused significant loss to human health across the globe. Its prevalence has been increasing every year and is one of the common malignancies in the case of organ transplant recipients, of which 95% constitute basal cell and squamous cell carcinomas. The prime factor causing skin cancer is UV radiation. Around the 20th century, sunlight was the primary cause of skin cancer. A novel hypothesis by US scientists stated that cutaneous melanoma was mainly due to recurrent exposure to the sun, whereas keratinocyte cancer occurred due to progressive accumulation of sun exposure. Management of skin cancer is done via various approaches, including cryotherapy, radiotherapy, and photodynamic therapy. Post-discovery of X-rays, radiotherapy has proven to treat skin cancers to some extent, but the indications are uncertain since it depends upon the type of tumour and surgical treatment required for the patient. Due to various limitations of skin cancer treatment and increased severity, there is a requirement for cost-effective, novel, and efficient treatment. Various nanocarriers such as SLNs, magnetic nanoparticles, gold nanoparticles, carbon nanotubes, etc., are the potential carriers in the management and prognosis of both non-melanoma and melanoma skin cancer. Various research and review databases and patent reports have been studied, and information compiled to extract the results. The review also discusses the role of various nanocarriers in treating and diagnosing skin cancer.
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Affiliation(s)
- Mehak Jindal
- Chitkara College of Pharmacy, Chitkara University, Chandigarh-Patiala National Highway, Rajpura, India
| | - Malkiet Kaur
- Chitkara College of Pharmacy, Chitkara University, Chandigarh-Patiala National Highway, Rajpura, India
| | - Manju Nagpal
- Chitkara College of Pharmacy, Chitkara University
| | - Manjinder Singh
- Chitkara College of Pharmacy, Chitkara University, Chandigarh-Patiala National Highway, Rajpura, India
| | - Geeta Aggarwal
- Delhi Pharmaceutical Sciences and Research University, Pushp Vihar, Sector-3 MB Road, New Delhi 110017, India
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15
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Inclusion complexation of emodin with various β-cyclodextrin derivatives: Preparation, characterization, molecular docking, and anticancer activity. J Mol Liq 2022. [DOI: 10.1016/j.molliq.2022.120314] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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16
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Pazopanib-laden lipid based nanovesicular delivery with augmented oral bioavailability and therapeutic efficacy against non-small cell lung cancer. Int J Pharm 2022; 628:122287. [DOI: 10.1016/j.ijpharm.2022.122287] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Revised: 09/15/2022] [Accepted: 10/08/2022] [Indexed: 11/18/2022]
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17
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Imran B, Din FU, Ali Z, Fatima A, Khan MW, Kim DW, Malik M, Sohail S, Batool S, Jawad M, Shabbir K, Zeb A, Khan BA. Statistically designed dexibuprofen loaded solid lipid nanoparticles for enhanced oral bioavailability. J Drug Deliv Sci Technol 2022. [DOI: 10.1016/j.jddst.2022.103904] [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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18
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Ouyang H, Hu J, Qiu X, Wu S, Guo F, Tan Y. Improved biopharmaceutical performance of antipsychotic drug using lipid nanoparticles via intraperitoneal route. Pharm Dev Technol 2022; 27:853-863. [PMID: 36124550 DOI: 10.1080/10837450.2022.2124521] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2022]
Abstract
This study aims to develop, characterize, and examine olanzapine-loaded solid lipid nanocarriers (OLAN-SLNs) for effective brain delivery. OLAN has poor water solubility and low penetration through blood-brain barrier (BBB). Herein, OLAN-SLNs were fabricated using high-pressure homogenization (HPH) method followed by their investigation for particle properties. Moreover, in vitro release and in vivo pharmacokinetics profiles of OLAN-SLNs were compared with pure drug. Anti-psychotic activity was performed in LPS-induced psychosis mice model. Furthermore, expressions of the COX-2 and NF-κB were measured trailed by histopathological examination. The optimized formulation demonstrated nanoparticle size (149.1 nm) with rounded morphology, negative zeta potential (-28.9 mV), lower PDI (0.334), and excellent entrapment efficiency (95%). OLAN-SLNs significantly retarded the drug release and showed sustained release pattern as compared to OLAN suspension. Significantly enhanced bioavailability (ninefold) was demonstrated in OLAN-SLNs when compared with OLAN suspension. Behavioral tests showed significantly less immobility and more struggling time in OLAN-SLNs treated mice group. Additionally, reduced expression of COX-2 and -NF κB in brain was found. Altogether, it can be concluded that SLNs have the potential to deliver active pharmaceutical ingredients to brain, most importantly to enhance their bioavailability and antipsychotic effect, as indicated for OLAN in this study.
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Affiliation(s)
- Hezhong Ouyang
- Department of Neurology, The People's Hospital of Danyang, Danyang, China
| | - Jinquan Hu
- Department of Neurology, Taihe Hospital, Hubei University of Medicine, Shiyan, China
| | - XingYing Qiu
- Department of Neurology, People's Liberation Army Joint Support Force 900th Hospital, Cangshan Hospital District, Fuzhou, China
| | - Shaochang Wu
- Department of Geriatrics, The Second People's Hospital of LiShui, Lishui, China
| | - Fudong Guo
- Department of Neurology, Affiliated Hospital of Chifeng University, Chifeng city, China
| | - Youguo Tan
- Department of Psychiatry, Zigong Mental health Centre, Zigong, China
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19
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Krajnović T, Pantelić NĐ, Wolf K, Eichhorn T, Maksimović-Ivanić D, Mijatović S, Wessjohann LA, Kaluđerović GN. Anticancer Potential of Xanthohumol and Isoxanthohumol Loaded into SBA-15 Mesoporous Silica Particles against B16F10 Melanoma Cells. MATERIALS 2022; 15:ma15145028. [PMID: 35888494 PMCID: PMC9320346 DOI: 10.3390/ma15145028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Revised: 07/06/2022] [Accepted: 07/14/2022] [Indexed: 11/16/2022]
Abstract
Xanthohumol (XN) and isoxanthohumol (IXN), prenylated flavonoids from Humulus lupulus, have been shown to possess antitumor/cancerprotective, antioxidant, antiinflammatory, and antiangiogenic properties. In this study, mesoporous silica (SBA-15) was loaded with different amounts of xanthohumol and isoxanthohumol and characterized by standard analytical methods. The anticancer potential of XN and IXN loaded into SBA-15 has been evaluated against malignant mouse melanoma B16F10 cells. When these cells were treated with SBA-15 containing xanthohumol, an increase of the activity correlated with a higher immobilization rate of XN was observed. Considering the amount of XN loaded into SBA-15 (calculated from TGA), an improved antitumor potential of XN was observed (IC50 = 10.8 ± 0.4 and 11.8 ± 0.5 µM for SBA-15|XN2 and SBA-15|XN3, respectively; vs. IC50 = 18.5 ± 1.5 µM for free XN). The main mechanism against tumor cells of immobilized XN includes inhibition of proliferation and autophagic cell death. The MC50 values for SBA-15 loaded with isoxanthohumol were over 300 µg/mL in all cases investigated.
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Affiliation(s)
- Tamara Krajnović
- Institute for Biological Research “Siniša Stanković”—National Institute of Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia; (T.K.); (D.M.-I.); (S.M.)
| | - Nebojša Đ. Pantelić
- Department of Engineering and Natural Sciences, University of Applied Sciences Merseburg, Eberhard-Leibnitz-Straße 2, 06217 Merseburg, Germany; (N.Đ.P.); (T.E.)
- Department of Chemistry and Biochemistry, Faculty of Agriculture, University of Belgrade, Nemanjina 6, 11080 Belgrade, Serbia
| | - Katharina Wolf
- Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Weinberg 3, 06120 Halle (Saale), Germany; (K.W.); (L.A.W.)
| | - Thomas Eichhorn
- Department of Engineering and Natural Sciences, University of Applied Sciences Merseburg, Eberhard-Leibnitz-Straße 2, 06217 Merseburg, Germany; (N.Đ.P.); (T.E.)
| | - Danijela Maksimović-Ivanić
- Institute for Biological Research “Siniša Stanković”—National Institute of Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia; (T.K.); (D.M.-I.); (S.M.)
| | - Sanja Mijatović
- Institute for Biological Research “Siniša Stanković”—National Institute of Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia; (T.K.); (D.M.-I.); (S.M.)
| | - Ludger A. Wessjohann
- Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Weinberg 3, 06120 Halle (Saale), Germany; (K.W.); (L.A.W.)
| | - Goran N. Kaluđerović
- Department of Engineering and Natural Sciences, University of Applied Sciences Merseburg, Eberhard-Leibnitz-Straße 2, 06217 Merseburg, Germany; (N.Đ.P.); (T.E.)
- Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Weinberg 3, 06120 Halle (Saale), Germany; (K.W.); (L.A.W.)
- Correspondence: ; Tel.: +49-3461-46-2012
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20
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Mahmud N, Anik MI, Hossain MK, Khan MI, Uddin S, Ashrafuzzaman M, Rahaman MM. Advances in Nanomaterial-Based Platforms to Combat COVID-19: Diagnostics, Preventions, Therapeutics, and Vaccine Developments. ACS APPLIED BIO MATERIALS 2022; 5:2431-2460. [PMID: 35583460 PMCID: PMC9128020 DOI: 10.1021/acsabm.2c00123] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Accepted: 04/24/2022] [Indexed: 12/12/2022]
Abstract
The COVID-19 pandemic caused by the SARS-CoV-2, a ribonucleic acid (RNA) virus that emerged less than two years ago but has caused nearly 6.1 million deaths to date. Recently developed variants of the SARS-CoV-2 virus have been shown to be more potent and expanded at a faster rate. Until now, there is no specific and effective treatment for SARS-CoV-2 in terms of reliable and sustainable recovery. Precaution, prevention, and vaccinations are the only ways to keep the pandemic situation under control. Medical and scientific professionals are now focusing on the repurposing of previous technology and trying to develop more fruitful methodologies to detect the presence of viruses, treat the patients, precautionary items, and vaccine developments. Nanomedicine or nanobased platforms can play a crucial role in these fronts. Researchers are working on many effective approaches by nanosized particles to combat SARS-CoV-2. The role of a nanobased platform to combat SARS-CoV-2 is extremely diverse (i.e., mark to personal protective suit, rapid diagnostic tool to targeted treatment, and vaccine developments). Although there are many theoretical possibilities of a nanobased platform to combat SARS-CoV-2, until now there is an inadequate number of research targeting SARS-CoV-2 to explore such scenarios. This unique mini-review aims to compile and elaborate on the recent advances of nanobased approaches from prevention, diagnostics, treatment to vaccine developments against SARS-CoV-2, and associated challenges.
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Affiliation(s)
- Niaz Mahmud
- Department of Biomedical Engineering,
Military Institute of Science and Technology, Dhaka 1216,
Bangladesh
| | - Muzahidul I. Anik
- Department of Chemical Engineering,
University of Rhode Island, Kingston, Rhode Island 02881,
United States
| | - M. Khalid Hossain
- Interdisciplinary Graduate School of Engineering
Science, Kyushu University, Fukuoka 816-8580,
Japan
- Atomic Energy Research Establishment,
Bangladesh Atomic Energy Commission, Dhaka 1349,
Bangladesh
| | - Md Ishak Khan
- Department of Neurosurgery, University of
Pennsylvania, Philadelphia, Pennsylvania 19104, United
States
| | - Shihab Uddin
- Department of Applied Chemistry, Graduate School of
Engineering, Kyushu University, Fukuoka 819-0395,
Japan
- Department of Chemical Engineering,
Massachusetts Institute of Technology, Cambridge
Massachusetts 02139, United States
| | - Md. Ashrafuzzaman
- Department of Biomedical Engineering,
Military Institute of Science and Technology, Dhaka 1216,
Bangladesh
| | - Md Mushfiqur Rahaman
- Department of Emergency Medicine, NYU
Langone Health, New York, New York 10016, United
States
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21
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Mennati A, Rostamizadeh K, Manjili HK, Fathi M, Danafar H. Co-delivery of siRNA and lycopene encapsulated hybrid lipid nanoparticles for dual silencing of insulin-like growth factor 1 receptor in MCF-7 breast cancer cell line. Int J Biol Macromol 2022; 200:335-349. [PMID: 34999039 DOI: 10.1016/j.ijbiomac.2021.12.197] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Revised: 12/29/2021] [Accepted: 12/31/2021] [Indexed: 12/12/2022]
Abstract
Insulin-like growth factor-1 receptor (IGF-1R) is expressed in malignant and normal breast tissue, and its intermittent activation by multiple IGF-1 signaling pathways leads to neoplasm cell proliferation, impaired apoptosis, increased survival, and resistance to cytotoxic therapeutic agents. Therefore, simultaneous suppression of the receptor and its cognate ligand would be a powerful promising strategy inhibiting malignant phenotypes of breast cancer cells. In the present study, Methoxypoly(ethylene glycol) - Poly(caprolactone) was hybridized with Dimethyldioctadecylammonium bromide (DDAB) cationic lipid (mPEG-PCL-DDAB) nanoparticles (NPs) and used as a carrier for simultaneous delivery of lycopene and insulin-like growth factor 1 receptor-specific lycopene encapsulated-mPEG-PCL-DDAB nanoparticle/siRNA to MCF-7 breast cancer cells. Then, the antitumor effects of this construct were evaluated in vitro. The results demonstrated that the synthesized mPEG-PCL-DDAB nanoparticle had suitable physicochemical properties. The use of mPEG-PCL-DDAB nanoparticle-loaded anti-insulin-like growth factor 1 receptor-siRNA and lycopene dramatically induced the process of apoptosis and arrested cell cycle in the MCF-7 tumor cell lines. In general, the findings of this study demonstrated the potency of mPEG-PCL-DDAB nanoparticles for dual delivery of siRNA, and lycopene in breast cancer cell lines followed the induction of apoptosis.
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Affiliation(s)
- Afsaneh Mennati
- Zanjan Pharmaceutical Nanotechnology Research Center, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran; Zanjan Pharmaceutical Biotechnology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran; Cancer Gene Therapy Research Center, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Kobra Rostamizadeh
- Zanjan Pharmaceutical Nanotechnology Research Center, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Hamidreza Kheiri Manjili
- Zanjan Pharmaceutical Biotechnology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Mojtaba Fathi
- Cancer Gene Therapy Research Center, Zanjan University of Medical Sciences, Zanjan, Iran; Department of Biochemistry and Genetics, Qazvin University of Medical Sciences, Qazvin, Iran.
| | - Hossein Danafar
- Zanjan Pharmaceutical Nanotechnology Research Center, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran; Zanjan Pharmaceutical Biotechnology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran.
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22
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Teja PK, Mithiya J, Kate AS, Bairwa K, Chauthe SK. Herbal nanomedicines: Recent advancements, challenges, opportunities and regulatory overview. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2022; 96:153890. [PMID: 35026510 DOI: 10.1016/j.phymed.2021.153890] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/18/2021] [Revised: 11/14/2021] [Accepted: 12/11/2021] [Indexed: 06/14/2023]
Abstract
BACKGROUND Herbal Nano Medicines (HNMs) are nano-sized medicine containing herbal drugs as extracts, enriched fractions or biomarker constituents. HNMs have certain advantages because of their increased bioavailability and reduced toxicities. There are very few literature reports that address the common challenges of herbal nanoformulations, such as selecting the type/class of nanoformulation for an extract or a phytochemical, selection and optimisation of preparation method and physicochemical parameters. Although researchers have shown more interest in this field in the last decade, there is still an urgent need for systematic analysis of HNMs. PURPOSE This review aims to provide the recent advancement in various herbal nanomedicines like polymeric herbal nanoparticles, solid lipid nanoparticles, phytosomes, nano-micelles, self-nano emulsifying drug delivery system, nanofibers, liposomes, dendrimers, ethosomes, nanoemulsion, nanosuspension, and carbon nanotube; their evaluation parameters, challenges, and opportunities. Additionally, regulatory aspects and future perspectives of herbal nanomedicines are also being covered to some extent. METHODS The scientific data provided in this review article are retrieved by a thorough analysis of numerous research and review articles, textbooks, and patents searched using the electronic search tools like Sci-Finder, ScienceDirect, PubMed, Elsevier, Google Scholar, ACS, Medline Plus and Web of Science. RESULTS In this review, the authors suggested the suitability of nanoformulation for a particular type of extracts or enriched fraction of phytoconstituents based on their solubility and permeability profile (similar to the BCS class of drugs). This review focuses on different strategies for optimising preparation methods for various HNMs to ensure reproducibility in context with all the physicochemical parameters like particle size, surface area, zeta potential, polydispersity index, entrapment efficiency, drug loading, and drug release, along with the consistent therapeutic index. CONCLUSION A combination of herbal medicine with nanotechnology can be an essential tool for the advancement of herbal medicine research with enhanced bioavailability and fewer toxicities. Despite the challenges related to traditional medicine's safe and effective use, there is huge scope for nanotechnology-based herbal medicines. Overall, it is well stabilized that herbal nanomedicines are safer, have higher bioavailability, and have enhanced therapeutic value than conventional herbal and synthetic drugs.
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Affiliation(s)
- Parusu Kavya Teja
- National Institute of Pharmaceutical Education and Research-Ahmedabad (NIPER-A), An Institute of National Importance, Government of India, Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Opp. Air Force Station, Palaj, Gandhinagar, 382355, Gujarat, India
| | - Jinal Mithiya
- National Institute of Pharmaceutical Education and Research-Ahmedabad (NIPER-A), An Institute of National Importance, Government of India, Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Opp. Air Force Station, Palaj, Gandhinagar, 382355, Gujarat, India
| | - Abhijeet S Kate
- National Institute of Pharmaceutical Education and Research-Ahmedabad (NIPER-A), An Institute of National Importance, Government of India, Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Opp. Air Force Station, Palaj, Gandhinagar, 382355, Gujarat, India
| | - Khemraj Bairwa
- National Institute of Pharmaceutical Education and Research-Ahmedabad (NIPER-A), An Institute of National Importance, Government of India, Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Opp. Air Force Station, Palaj, Gandhinagar, 382355, Gujarat, India..
| | - Siddheshwar K Chauthe
- National Institute of Pharmaceutical Education and Research-Ahmedabad (NIPER-A), An Institute of National Importance, Government of India, Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Opp. Air Force Station, Palaj, Gandhinagar, 382355, Gujarat, India..
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Eissa MA, Hashim YZHY, Mohd Nasir MH, Nor YA, Salleh HM, Isa MLM, Abd-Azziz SSS, Abd Warif NM, Ramadan E, Badawi NM. Fabrication and characterization of Agarwood extract-loaded nanocapsules and evaluation of their toxicity and anti-inflammatory activity on RAW 264.7 cells and in zebrafish embryos. Drug Deliv 2021; 28:2618-2633. [PMID: 34894947 PMCID: PMC8676596 DOI: 10.1080/10717544.2021.2012307] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Aquilaria malaccensis has been traditionally used to treat several medical disorders including inflammation. However, the traditional claims of this plant as an anti-inflammatory agent has not been substantially evaluated using modern scientific techniques. The main objective of this study was to evaluate the anti-inflammatory effect of Aquilaria malacensis leaf extract (ALEX-M) and potentiate its activity through nano-encapsulation. The extract-loaded nanocapsules were fabricated using water-in-oil-in-water (w/o/w) emulsion method and characterized via multiple techniques including DLS, TEM, FTIR, and TGA. The toxicity and the anti-inflammatory activity of ALEX-M and the extract-loaded nanocapsules (ALEX-M-PNCs) were evaluated in-vitro on RAW 264.7 macrophages and in-vivo on zebrafish embryos. The nanocapsules demonstrated spherical shape with mean particle diameter of 167.13 ± 1.24 nm, narrow size distribution (PDI = 0.29 ± 0.01), and high encapsulation efficiency (87.36 ± 1.81%). ALEX-M demonstrated high viability at high concentrations in RAW 264.7 cells and zebrafish embryos, however, ALEX-M-PNCs showed relatively higher cytotoxicity. Both free and nanoencapsulated extract expressed anti-inflammatory effects through significant reduction of the pro-inflammatory mediator nitric oxide (NO) production in LPS/IFNγ-stimulated RAW 264.7 macrophages and zebrafish embryos in a concentration-dependent manner. The findings highlight that ALEX-M can be recognized as a potential anti-inflammatory agent, and its anti-inflammatory activity can be potentiated by nano-encapsulation. Further studies are warranted toward investigation of the mechanistic and immunomodulatory roles of ALEX-M.
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Affiliation(s)
- Manar A Eissa
- International Institute for Halal Research and Training (INHART), International Islamic University Malaysia (IIUM), Kuala Lumpur, Malaysia.,Center for Drug Research and Development (CDRD), The British University in Egypt (BUE), Cairo, Egypt
| | - Yumi Z H-Y Hashim
- International Institute for Halal Research and Training (INHART), International Islamic University Malaysia (IIUM), Kuala Lumpur, Malaysia
| | - Mohd Hamzah Mohd Nasir
- Department of Biotechnology, Kulliyyah of Science, International Islamic University Malaysia (IIUM), Kuantan, Pahang, Malaysia.,Central Research and Animal Facility (CREAM), Kulliyyah of Science, International Islamic University Malaysia (IIUM), Kuantan, Pahang, Malaysia
| | - Yusilawati Ahmad Nor
- Department of Biotechnology Engineering, Kulliyyah of Engineering, International Islamic University Malaysia (IIUM), Kuala Lumpur, Malaysia
| | - Hamzah Mohd Salleh
- International Institute for Halal Research and Training (INHART), International Islamic University Malaysia (IIUM), Kuala Lumpur, Malaysia
| | - Muhammad Lokman Md Isa
- Kulliyah of Nursing, International Islamic University Malaysia (IIUM), Jalan Sultan Ahmad Shah, Kuantan, Pahang, Malaysia
| | - Saripah S S Abd-Azziz
- Faculty of Science and Mathematics, Sultan Idris Education University, Perak, Tanjung Malim, Malaysia
| | - Nor Malia Abd Warif
- Biomedical Sciences Program, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Eman Ramadan
- Center for Drug Research and Development (CDRD), The British University in Egypt (BUE), Cairo, Egypt.,Department of Pharmacology and Toxicology, Faculty of Pharmacy, The British University in Egypt (BUE), Cairo, Egypt
| | - Noha M Badawi
- Center for Drug Research and Development (CDRD), The British University in Egypt (BUE), Cairo, Egypt.,Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, The British University in Egypt (BUE), Cairo, Egypt
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Handa M, Beg S, Shukla R, Barkat MA, Choudhry H, Singh KK. Recent advances in lipid-engineered multifunctional nanophytomedicines for cancer targeting. J Control Release 2021; 340:48-59. [PMID: 34695523 DOI: 10.1016/j.jconrel.2021.10.025] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2021] [Revised: 10/19/2021] [Accepted: 10/20/2021] [Indexed: 12/12/2022]
Abstract
Cancer is a leading cause of death in many countries around the world. However, the efficacy of current treatments available for variety of cancers is considered to be suboptimal due to the pathophysiological challenges associated with the disease which limits the efficacy of the anticancer drugs. Moreover, the vulnerability towards off-target effects and high toxicity also limits the use of drugs for the treatment of cancers. Besides, the biopharmaceutical challenges like poor water solubility and permeability of the drugs, along with the absence of active targeting capability further decreases the utility of drugs in cancer therapy. As a result of these deficiencies, the current therapeutic strategies face noncompliance to patients for providing meaningful benefits after administration. With the advancements in nanotechnology, there has been a paradigm shift in the modalities for cancer treatment with the help of phytomedicine-based nanosized drug delivery systems coupled with variegated surface-engineering strategies for targeted drug delivery. Among these delivery systems, lipid-based nanoparticles are considered as one of the highly biocompatible, efficient and effective systems extensively explored for anticancer drug delivery. These include diverse range of systems including liposomes, nanoemulsions, solid lipid nanoparticles, nanostructured lipidic carriers and supramolecular carriers, which alters pharmacokinetic and biodistribution of the drugs for active targeting to the desired site of action by overcoming the biopharmaceutical challenges associated with anticancer drug delivery. The present review endeavours to provide a comprehensive account on the recent advances in the application of lipid-based nanostructured systems for improving the pharmacotherapeutic performance of phytomedicines for cancer targeting application.
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Affiliation(s)
- Mayank Handa
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research-Raebareli, Lucknow 226002, U.P., India
| | - Sarwar Beg
- School of Pharmacy and Biomedical Sciences, Faculty of Clinical and Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, UK; Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard University, New Delhi 110062, India.
| | - Rahul Shukla
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research-Raebareli, Lucknow 226002, U.P., India.
| | - Md Abul Barkat
- Department of Pharmaceutics, College of Pharmacy, University of Hafr Al Batin, Al Jamiah, Hafr Al Batin 39524, Saudi Arabia
| | - Hani Choudhry
- Department of Biochemistry, Cancer Metabolism & Epigenetic Unit, Faculty of Science, King Fahd Center for Medical Research, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Kamalinder K Singh
- School of Pharmacy and Biomedical Sciences, Faculty of Clinical and Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, UK.
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Semwal RB, Semwal DK, Combrinck S, Viljoen A. Emodin - A natural anthraquinone derivative with diverse pharmacological activities. PHYTOCHEMISTRY 2021; 190:112854. [PMID: 34311280 DOI: 10.1016/j.phytochem.2021.112854] [Citation(s) in RCA: 88] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 06/19/2021] [Accepted: 06/20/2021] [Indexed: 06/13/2023]
Abstract
Emodin (1,3,8-trihydroxy-6-methyl-anthraquinone) is a natural anthraquinone derivative that is present in numerous globally renowned herbal medicines. It is recognised as a protein tyrosine kinase inhibitor and as an anticancer drug, active against various tumour cells, including lung, breast, liver, and ovarian cancer cells. Recently, its role in combination chemotherapy with various allopathic medicines, to minimize their toxicity and to enhance their efficacy, has been studied. The use of emodin in these therapies is gaining popularity, due to fewer associated side effects compared with standard anticancer drugs. Emodin has a broad therapeutic window, and in addition to its antineoplastic activity, it displays anti-ulcer, anti-inflammatory, hepatoprotective, neuroprotective, antimicrobial, muscle relaxant, immunosuppressive and antifibrotic activities, in both in vitro and in vivo models. Although reviews on the anticancer activity of emodin have been published, none coherently unite all the pharmacological properties of emodin, particularly the anti-oxidant, antimicrobial, antidiabetic, immunosuppressive and hepatoprotective activities of the compound. Hence, in this review, all of the available data regarding the pharmacological properties of emodin are explored, with particular emphasis on the modes of action of the molecule. In addition, the manuscript details the occurrence, biosynthesis and chemical synthesis of the compound, as well as its toxic effects on biotic systems.
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Affiliation(s)
- Ruchi Badoni Semwal
- Department of Pharmaceutical Sciences, Faculty of Science, Tshwane University of Technology, Private Bag X680, Pretoria, 0001, South Africa; Department of Chemistry, Pt. Lalit Mohan Sharma Govt. Post Graduate College, Rishikesh, 249201, India
| | - Deepak Kumar Semwal
- Department of Pharmaceutical Sciences, Faculty of Science, Tshwane University of Technology, Private Bag X680, Pretoria, 0001, South Africa; Department of Phytochemistry, Faculty of Biomedical Sciences, Uttarakhand Ayurved University, Harrawala, Dehradun, 248001, India
| | - Sandra Combrinck
- Department of Pharmaceutical Sciences, Faculty of Science, Tshwane University of Technology, Private Bag X680, Pretoria, 0001, South Africa
| | - Alvaro Viljoen
- Department of Pharmaceutical Sciences, Faculty of Science, Tshwane University of Technology, Private Bag X680, Pretoria, 0001, South Africa; SAMRC Herbal Drugs Research Unit, Faculty of Science, Tshwane University of Technology, Private Bag X680, Pretoria, 0001, South Africa.
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Zou T, Lan M, Liu F, Li L, Cai T, Tian H, Cai Y. Emodin-loaded polymer-lipid hybrid nanoparticles enhance the sensitivity of breast cancer to doxorubicin by inhibiting epithelial–mesenchymal transition. Cancer Nanotechnol 2021. [DOI: 10.1186/s12645-021-00093-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Abstract
Background
The role of epithelial–mesenchymal transition (EMT) involved in breast cancer metastasis and chemoresistance has been increasingly recognized. However, it is necessary to search for more effective strategies to inhibit EMT thereby increase the sensitivity of breast cancer cells to chemotherapy drugs. Emodin has a potential in overcoming tumor drug resistance and restraining the development of EMT, but the poor internalization into breast cancer cells limited the application.
Results
MCF-7/ADR cells have more EMT characteristics than MCF-7 cell. EMT in MCF-7/ADR cells promotes the development of drug resistance via apoptosis resistance and facilitating the expression of P-gp. The anti-cancer effect of DOX enhanced by the decreasing of drug resistance protein P-gp and apoptosis-related proteins after EMT inhibited in MCF-7/ADR cells. E-PLNs increase the cellular uptake of EMO and restore DOX sensitivity in MCF-7/ADR cells by inhibiting EMT.
Conclusion
E-PLNs inhibit EMT to enhance the sensitivity of breast cancer to DOX. The combination of E-PLNs and DOX can improve the efficacy of DOX in the treatment of breast cancer, which provides a new method to prevent or delay clinical drug resistance.
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Tuli HS, Aggarwal V, Tuorkey M, Aggarwal D, Parashar NC, Varol M, Savla R, Kaur G, Mittal S, Sak K. Emodin: A metabolite that exhibits anti-neoplastic activities by modulating multiple oncogenic targets. Toxicol In Vitro 2021; 73:105142. [PMID: 33722736 DOI: 10.1016/j.tiv.2021.105142] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Revised: 02/11/2021] [Accepted: 03/09/2021] [Indexed: 12/19/2022]
Abstract
Oncogenic transformation has been the major cause of global mortality since decades. Despite established therapeutic regimes, majority of cancer patients either present with tumor relapse, refractory disease or therapeutic resistance. Numerous drug candidates are being explored to tap the key reason being poor tumor remission rates, from novel chemotherapy agents to immunotherapy to exploring natural compound derivatives with effective anti-cancer potential. One of these natural product metabolites, emodin has present with significant potential to target tumor oncogenic processes: induction of apoptosis and cell cycle arrest, tumor angiogenesis, and metastasis to chemoresistance in malignant cells. Based on the present scientific excerpts on safety and effectiveness of emodin in targeting hallmarks of tumor progression, emodin is being promisingly explored using nanotechnology platforms for long-term sustained treatment and management of cancer patients. In this review, we summarize the up-to-date scientific literature supporting the anti-neoplastic potential of emodin. We also provide an insight into toxicity and safety profile of emodin and how emodin has emerged as an effective therapeutic alternative in synergism with established conventional chemotherapeutic regimes for management and treatment of tumor progression.
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Affiliation(s)
- Hardeep Singh Tuli
- Department of Biotechnology, Maharishi Markandeshwar (Deemed to be University), Mullana-Ambala, Haryana 133207, India.
| | - Vaishali Aggarwal
- Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, USA
| | - Muobarak Tuorkey
- Division of Physiology, Zoology Department, Faculty of Science, Damanhour University, Damanhour, Egypt
| | - Diwakar Aggarwal
- Department of Biotechnology, Maharishi Markandeshwar (Deemed to be University), Mullana-Ambala, Haryana 133207, India
| | | | - Mehmet Varol
- Department of Molecular Biology and Genetics, Faculty of Science, Kotekli Campus, Mugla Sitki Kocman University, Mugla TR48000, Turkey
| | - Raj Savla
- Shobhaben Pratapbhai Patel School of Pharmacy and Technology Management, SVKM's NMIMS, Mumbai 56, Maharashtra, India
| | - Ginpreet Kaur
- Shobhaben Pratapbhai Patel School of Pharmacy and Technology Management, SVKM's NMIMS, Mumbai 56, Maharashtra, India
| | - Sonam Mittal
- School of Biotechnology, Jawaharlal Nehru University, New Delhi 110067, India
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Is Emodin with Anticancer Effects Completely Innocent? Two Sides of the Coin. Cancers (Basel) 2021; 13:cancers13112733. [PMID: 34073059 PMCID: PMC8198870 DOI: 10.3390/cancers13112733] [Citation(s) in RCA: 62] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Revised: 05/25/2021] [Accepted: 05/28/2021] [Indexed: 12/12/2022] Open
Abstract
Many anticancer active compounds are known to have the capacity to destroy pathologically proliferating cancer cells in the body, as well as to destroy rapidly proliferating normal cells. Despite remarkable advances in cancer research over the past few decades, the inclusion of natural compounds in researches as potential drug candidates is becoming increasingly important. However, the perception that the natural is reliable is an issue that needs to be clarified. Among the various chemical classes of natural products, anthraquinones have many biological activities and have also been proven to exhibit a unique anticancer activity. Emodin, an anthraquinone derivative, is a natural compound found in the roots and rhizomes of many plants. The anticancer property of emodin, a broad-spectrum inhibitory agent of cancer cells, has been detailed in many biological pathways. In cancer cells, these molecular mechanisms consist of suppressing cell growth and proliferation through the attenuation of oncogenic growth signaling, such as protein kinase B (AKT), mitogen-activated protein kinase (MAPK), HER-2 tyrosine kinase, Wnt/-catenin, and phosphatidylinositol 3-kinase (PI3K). However, it is known that emodin, which shows toxicity to cancer cells, may cause kidney toxicity, hepatotoxicity, and reproductive toxicity especially at high doses and long-term use. At the same time, studies of emodin, which has poor oral bioavailability, to transform this disadvantage into an advantage with nano-carrier systems reveal that natural compounds are not always directly usable compounds. Consequently, this review aimed to shed light on the anti-proliferative and anti-carcinogenic properties of emodin, as well as its potential toxicities and the advantages of drug delivery systems on bioavailability.
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Mutingwende FP, Kondiah PPD, Ubanako P, Marimuthu T, Choonara YE. Advances in Nano-Enabled Platforms for the Treatment of Depression. Polymers (Basel) 2021; 13:polym13091431. [PMID: 33946703 PMCID: PMC8124207 DOI: 10.3390/polym13091431] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 04/07/2021] [Accepted: 04/19/2021] [Indexed: 01/10/2023] Open
Abstract
Nanotechnology has aided in the advancement of drug delivery for the treatment of several neurological disorders including depression. Depression is a relatively common mental disorder which is characterized by a severe imbalance of neurotransmitters. Several current therapeutic regimens against depression display drawbacks which include low bioavailability, delayed therapeutic outcome, undesirable side effects and drug toxicity due to high doses. The blood–brain barrier limits the entry of the drugs into the brain matrix, resulting in low bioavailability and tissue damage due to drug accumulation. Due to their size and physico-chemical properties, nanotechnological drug delivery systems present a promising strategy to enhance the delivery of nanomedicines into the brain matrix, thereby improving bioavailability and limiting toxicity. Furthermore, ligand-complexed nanocarriers can improve drug specificity and antidepressant efficacy and reduce drug toxicity. Biopolymers and nanocarriers can also be employed to enhance controlled drug release and reduce the hepatic first-pass effect, hence reducing the dosing frequency. This manuscript reviews recent advances in different biopolymers, such as polysaccharides and other nanocarriers, for targeted antidepressant drug delivery to the brain. It probes nano-based strategies that can be employed to enhance the therapeutic efficacy of antidepressants through the oral, intranasal, and parenteral routes of administration.
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Badawi NM, Elkafrawy MA, Yehia RM, Attia DA. Clinical comparative study of optimized metronidazole loaded lipid nanocarrier vaginal emulgel for management of bacterial vaginosis and its recurrence. Drug Deliv 2021; 28:814-825. [PMID: 33899634 PMCID: PMC8086592 DOI: 10.1080/10717544.2021.1912211] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
The main focus of the current work was to design, evaluate and clinically compare the efficiency of novel metronidazole (MTD) loaded solid lipid nanoparticles (SLNs) vaginal emulgel with the marketed vaginal gel (Metron®) against Bacterial vaginosis (BV). Eight formulations were fabricated using 23 full factorial design and prepared by stearic acid and tween 80 as solid lipid and surfactant, respectively. Lipid and surfactant concentrations in addition to sonication amplitude were chosen as the independent variables (X1–X3). Then, the prepared MTD loaded SLNs were evaluated based on the dependent variables which were particle size, polydispersity index, zeta potential, entrapment efficiency, and cumulative % drug release for 24 h (Y1–Y5). The in vitro release study exhibited a sustained release of MTD from the SLNs up to 24 h. The optimal MTD loaded SLNs showed nanosized particles (256 nm) with EE% (52%), and an acceptable ZP value (−29.5 mV). Also, the optimized MTD-SLNs formulation was incorporated into Carbopol emulgel and investigated clinically for its effect against BV. Clinical studies recorded significant enhancement in therapeutic response of MTD from optimized SLNs vaginal emulgel formulation regarding the clinical treatment (p < .05) and low recurrence rate (p < .001) against the marketed product. In conclusion, our findings recommend that the fabricated MTD loaded SLNs vaginal emulgel have significant therapeutic effect in terms of BV management over commercially obtainable marketed vaginal gel (Metron®).
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Affiliation(s)
- Noha M Badawi
- Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, The British University in Egypt (BUE), Cairo, Egypt
| | - Mona A Elkafrawy
- Department of Obstetrics and Gynecology, Faculty of Medicine (Girls), Al-Azhar University, Cairo, Egypt
| | - Rania M Yehia
- Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, The British University in Egypt (BUE), Cairo, Egypt
| | - Dalia A Attia
- Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, The British University in Egypt (BUE), Cairo, Egypt
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Polymeric Lipid Hybrid Nanoparticles as a Delivery System Enhance the Antitumor Effect of Emodin in Vitro and in Vivo. J Pharm Sci 2021; 110:2986-2996. [PMID: 33864779 DOI: 10.1016/j.xphs.2021.04.006] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 03/31/2021] [Accepted: 04/12/2021] [Indexed: 01/10/2023]
Abstract
This study aimed to evaluate the therapeutic efficacy of Emodin-loaded polymer lipid hybrid nanoparticles (E-PLNs) for breast cancer. The size, Zeta potential, surface morphology, encapsulation efficiency, stability, in vitro drug release of E-PLNs prepared by the nanoprecipitation method were characterized. The uptake, in-vitro cytotoxicities and apoptosis of free drug, E-PLNs were investigated against MCF-7 cells. The efficacy of E-PLNs in tumor bearing nude mice has also been studied.The average particle size of the experimentally prepared E-PLNs was (122.7±1.79) nm, and the encapsulation rate was 72.8%. Compared with free Emodin (EMO), E-PLNs showed greater toxicity to MCF-7 cells by promoting the uptake of EMO, and can promote the early apoptosis of MCF-7 cells. In addition to the morphological changes of apoptotic cells, the ratio of Bax/Bcl-2 was significantly increased, which indicated that E-PLNs can induce apoptosis in MCF-7 cells to achieve anticancer effect. Finally, E-PLNs significantly inhibited tumor growth by more than 60%, which may be related to its passive targeting effect on tumor site. Our results suggest that E-PLNs have shown good anti-breast cancer effect than free EMO. Moreover, the effect of E-PLNs on MCF-7 cells is mainly related to the induction of apoptosis.
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Talib WH, Alsalahat I, Daoud S, Abutayeh RF, Mahmod AI. Plant-Derived Natural Products in Cancer Research: Extraction, Mechanism of Action, and Drug Formulation. Molecules 2020; 25:E5319. [PMID: 33202681 PMCID: PMC7696819 DOI: 10.3390/molecules25225319] [Citation(s) in RCA: 61] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Revised: 11/10/2020] [Accepted: 11/11/2020] [Indexed: 12/24/2022] Open
Abstract
Cancer is one of the main causes of death globally and considered as a major challenge for the public health system. The high toxicity and the lack of selectivity of conventional anticancer therapies make the search for alternative treatments a priority. In this review, we describe the main plant-derived natural products used as anticancer agents. Natural sources, extraction methods, anticancer mechanisms, clinical studies, and pharmaceutical formulation are discussed in this review. Studies covered by this review should provide a solid foundation for researchers and physicians to enhance basic and clinical research on developing alternative anticancer therapies.
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Affiliation(s)
- Wamidh H. Talib
- Department of Clinical Pharmacy and Therapeutics, Applied Science Private University, Amman 11931, Jordan;
| | - Izzeddin Alsalahat
- Department of Pharmaceutical Chemistry and Pharmacognosy, Applied Science Private University, Amman 11931, Jordan; (I.A.); (S.D.); (R.F.A.)
| | - Safa Daoud
- Department of Pharmaceutical Chemistry and Pharmacognosy, Applied Science Private University, Amman 11931, Jordan; (I.A.); (S.D.); (R.F.A.)
| | - Reem Fawaz Abutayeh
- Department of Pharmaceutical Chemistry and Pharmacognosy, Applied Science Private University, Amman 11931, Jordan; (I.A.); (S.D.); (R.F.A.)
| | - Asma Ismail Mahmod
- Department of Clinical Pharmacy and Therapeutics, Applied Science Private University, Amman 11931, Jordan;
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33
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Correlation between assembly structure of a gamma irradiated albumin nanoparticle and its function as a drug delivery system. Colloids Surf A Physicochem Eng Asp 2020. [DOI: 10.1016/j.colsurfa.2020.125176] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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Tan L, Deng X, Lai X, Zeng T, Li A, Hu J, Xiong Z. Mesoscale nanoparticles encapsulated with emodin for targeting antifibrosis in animal models. OPEN CHEM 2020. [DOI: 10.1515/chem-2020-0163] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
AbstractThe aim of this study is to explore the kidney-targeting capability of mesoscale nanoparticles (MNPs)-emodin (Em-MNPs) and its potential antifibrosis in the animal model. First, MNPs and Em-MNPs were synthesized via nanoprecipitation method, and their diameters were both ∼400 nm with the uniform size. The entrapment efficiency of MNPs was 45.1% when adding emodin at the concentration of 12 mg/mL. Moreover, cytotoxicity assay showed that Em-MNPs presented excellent biocompatibility in rat proximal tubular cells. Cellular uptake assay demonstrated that Em-MNPs had high-efficiency uptake, especially in the cytoplasm. Ex vivo organ fluorescence imaging revealed that Em-MNPs possessed specific kidney-targeting ability with relative long retention time in the kidney (∼24 h). In the renal unilateral ureteral obstruction model, Em-MNPs treatment could significantly alleviate kidney tubule injury and reduce extracellular matrix deposition compared with free MNPs. Herein, Em-MNPs with specific kidney-targeting and preferable antifibrosis effects in animal model may pave an avenue for treating renal diseases.
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Affiliation(s)
- Lishan Tan
- Department of Nephrology, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong, 518036, China
| | - Xiulong Deng
- Department of Chemical and Chemical Engineering, Key Laboratory of Organo-Pharmaceutical Chemistry, Gannan Normal University, Ganzhou, Jiangxi Province, 341000, China
| | - Xuandi Lai
- Department of Oncology, Peking University Shenzhen Hospital, Shenzhen, Guangdong, 518036, China
| | - Tao Zeng
- Department of Nephrology, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China
| | - Aiqing Li
- Department of Nephrology, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China
| | - Jianqiang Hu
- Department of Nephrology, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China
| | - Zuying Xiong
- Department of Nephrology, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong, 518036, China
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Badawi N, El-Say K, Attia D, El-Nabarawi M, Elmazar M, Teaima M. Development of Pomegranate Extract-Loaded Solid Lipid Nanoparticles: Quality by Design Approach to Screen the Variables Affecting the Quality Attributes and Characterization. ACS OMEGA 2020; 5:21712-21721. [PMID: 32905321 PMCID: PMC7469390 DOI: 10.1021/acsomega.0c02618] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Accepted: 08/03/2020] [Indexed: 06/11/2023]
Abstract
The aim of this work was to study the influence of process variables on the quality attributes of pomegranate extract loaded solid lipid nanoparticles (PE-SLNs) using Plackett-Burman design. PE-SLN formulations were prepared by hot homogenization followed by ultra-sonication technique and evaluated based on the dependent variables that were analyzed utilizing Statgraphics Centurion XV software. The lipid and surfactant (type and concentration), co-surfactant concentration, sonication time, and amplitude were selected as the independent variables (X 1-X 7). The dependent parameters were particle size, polydispersity index, zeta potential, entrapment efficiency, and cumulative drug release (Y 1-Y 5). Response surface plots, Pareto charts, and mathematical equations were generated to study the influence of independent variables on the dependent quality parameters. Out of seven variables, X 1, X 2, and X 6 have the main significant (p value < 0.05) effect on the entrapment efficiency, the cumulative drug release, the polydispersity index, respectively, while particle size was mainly affected by X 3, X 6 and zeta potential by X 1, X 3, and X 4. Consequently, this screening study revealed that stearic acid as lipid, Tween 80 as surfactant, as well as sonication with short time and high amplitude can be selected for the development of PE-SLN formulation with minimum particle size, maximum zeta potential, highest entrapment, and sustained drug release behavior. Meanwhile, concentrations of lipid, surfactant, and co-surfactant are planned to be scaled up for further optimization study. In conclusion, the Plackett-Burman design verified its influence and significance in determining and understanding both process and formulation variables affecting the quality of PE-SLNs.
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Affiliation(s)
- Noha Badawi
- Department
of Pharmaceutics, Faculty of Pharmacy, The
British University in Egypt, P.O. Box 11837, Cairo 11837, Egypt
| | - Khalid El-Say
- Department
of Pharmaceutics, King Abdulaziz University, P.O. Box 80260, Jeddah 21589, Saudi Arabia
- Department
of Pharmaceutics, Faculty of Pharmacy, Al-Azhar
University, Cairo 11651, Egypt
| | - Dalia Attia
- Department
of Pharmaceutics, Faculty of Pharmacy, The
British University in Egypt, P.O. Box 11837, Cairo 11837, Egypt
| | - Mohamed El-Nabarawi
- Department
of Pharmaceutics, Faculty of Pharmacy, Cairo
University, P.O. Box 11562, Cairo 12411, Egypt
| | - Mohey Elmazar
- Department
of Pharmacology, Faculty of Pharmacy, The
British University in Egypt, P.O. Box 11837, Cairo 11837, Egypt
| | - Mahmoud Teaima
- Department
of Pharmaceutics, Faculty of Pharmacy, Cairo
University, P.O. Box 11562, Cairo 12411, Egypt
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dos Santos IMD, Pereira SP, Mezacasa AV, Caceres OIA, Timoteo F, Lopes AS, del Pino KF, Duarte AP, Cardoso TFM, de Castro GR, Rashid HU, Martines MAU. Emodin-Containing MCM-41 Type Mesoporous Silica Nanoparticle Drug Delivery System. THEOR EXP CHEM+ 2020. [DOI: 10.1007/s11237-020-09649-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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Ribeiro AF, Santos JF, Mattos RR, Barros EGO, Nasciutti LE, Cabral LM, Sousa VPDE. Characterization and in vitro antitumor activity of polymeric nanoparticles loaded with Uncaria tomentosa extract. AN ACAD BRAS CIENC 2020; 92:e20190336. [PMID: 32321026 DOI: 10.1590/0001-3765202020190336] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2019] [Accepted: 08/05/2019] [Indexed: 11/22/2022] Open
Abstract
Uncaria tomentosa (UT) extracts have been shown to have promising anti-tumor activity. We hypothesized that its incorporation into nanostructured systems could improve the anticancer properties. Here, poly-e-caprolactone (PCL) and poly-d,l-lactide-co-glycolide (PLGA) were employed to generate nanoparticles loaded with UT extract in a single emulsion solvent evaporation method. The nanoparticles were characterized by particle size, zeta potential, morphology and entrapment efficiency along with stability and release profiles. The nanoparticles presented entrapment efficiencies above 60% and a mean diameter below 300nm. UT-PCL nanoparticles presented higher entrapment efficiency and mean particle size as well as a slow release rate. The UT-PLGA nanoparticles showed higher drug loading. Two prostate cancer cell-lines, LNCaP and DU145 that were derived from metastatic sites, served as model systems to assess cytotoxicity and anti-cancer activity. In vitro, both formulations reduced the viability of DU145 and LNCaP cells. Yet, the UT-PLGA nanoparticles showed higher cytotoxicity towards DU145 cells while the UTPCL against LNCaP cells. The results confirm that the incorporation of UT into nanoparticles could enhance its anti-cancer activities that can offer a viable alternative for the treatment of prostrate canner and highlights the potential of nanostructured systems to provide a promising methodology to enhance the activity of natural extracts.
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Affiliation(s)
- Ana F Ribeiro
- Departamento de Fármacos e Medicamentos, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373, CCS, 21941-902 Rio de Janeiro, RJ, Brazil.,Faculdade de Farmácia, Federal Institute of Education, Science and Technology of Rio de Janeiro, Rua Professor Carlos Wenceslau, 343, 21715-000 Rio de Janeiro, RJ, Brazil
| | - Juliana F Santos
- Faculdade de Farmácia, Federal Institute of Education, Science and Technology of Rio de Janeiro, Rua Professor Carlos Wenceslau, 343, 21715-000 Rio de Janeiro, RJ, Brazil
| | - Rômulo R Mattos
- Programa de pesquisa em Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373, CCS, 21941-902 Rio de Janeiro, RJ, Brazil
| | - Eliane G O Barros
- Programa de pesquisa em Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373, CCS, 21941-902 Rio de Janeiro, RJ, Brazil
| | - Luiz Eurico Nasciutti
- Programa de pesquisa em Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373, CCS, 21941-902 Rio de Janeiro, RJ, Brazil
| | - Lúcio M Cabral
- Departamento de Fármacos e Medicamentos, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373, CCS, 21941-902 Rio de Janeiro, RJ, Brazil
| | - Valeria P DE Sousa
- Departamento de Fármacos e Medicamentos, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373, CCS, 21941-902 Rio de Janeiro, RJ, Brazil
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Khaleeq N, Din FU, Khan AS, Rabia S, Dar J, Khan GM. Development of levosulpiride-loaded solid lipid nanoparticles and their in vitro and in vivo comparison with commercial product. J Microencapsul 2020; 37:160-169. [PMID: 31916886 DOI: 10.1080/02652048.2020.1713242] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
The aim of this study was to develop levosulpiride-loaded solid lipid nanoparticles (SLNs) with enhanced solubilisation and bioavailability. The levosulpiride loaded-SLNs were composed of levosulpiride, stearic acid, and tween 80 in their respective weight ratios of (1, 5, and 1.5 mg) dissolved in 1 ml distilled water. Physicochemical properties of the SLNs such as particle size, shape, crystallinity, and chemical interaction were evaluated. Further, the in vitro drug dissolution, pharmacokinetic and stability studies of the SLNs were performed. The SLNs were rounded shaped stable nanoparticles with average diameter of 200 nm. They demonstrate 1.5- and 3-fold better drug dissolution when compared with the commercial product and levosulpiride powder, respectively. The SLNs enhanced the bioavailability of levosulpiride 3 times and 7 times, respectively, when compared with the commercial product and levosulpiride powder. It can be concluded that SLNs are capable to improve the dissolution and bioavailability of levosulpiride, even more than the commercial product.
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Affiliation(s)
- Nadra Khaleeq
- Department of Pharmacy, Faculty of biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan
| | - Fakhar-Ud Din
- Department of Pharmacy, Faculty of biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan
| | - Anam Sajjad Khan
- Department of Pharmacy, Faculty of biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan
| | - Samreen Rabia
- Department of Pharmacy, Faculty of biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan
| | - Junaid Dar
- Department of Pharmacy, Faculty of biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan
| | - Gul Majid Khan
- Department of Pharmacy, Faculty of biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan
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Vaiserman A, Koliada A, Zayachkivska A, Lushchak O. Nanodelivery of Natural Antioxidants: An Anti-aging Perspective. Front Bioeng Biotechnol 2020; 7:447. [PMID: 31998711 PMCID: PMC6965023 DOI: 10.3389/fbioe.2019.00447] [Citation(s) in RCA: 103] [Impact Index Per Article: 20.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Accepted: 12/12/2019] [Indexed: 12/11/2022] Open
Abstract
The aging process is known to be associated with heightened oxidative stress and related systemic inflammation. Therefore, antioxidant supplementation is regarded as a promising strategy to combat aging and associated pathological conditions. Food-grade antioxidants from plant-derived extracts are the most common ingredients of these supplements. Phyto-bioactive compounds such as curcumin, resveratrol, catechins, quercetin are among the most commonly applied natural compounds used as potential modulators of the free radical-induced cellular damages. The therapeutic potential of these compounds is, however, restricted by their low bioavailability related to poor solubility, stability, and absorbance in gastrointestinal tract. Recently, novel nanotechnology-based systems were developed for therapeutic delivery of natural antioxidants with improved bioavailability and, consequently, efficacy in clinical practice. Such systems have provided many benefits in preclinical research over the conventional preparations, including superior solubility and stability, extended half-life, improved epithelium permeability and bioavailability, enhanced tissue targeting, and minimized side effects. The present review summarizes recent developments in nanodelivery of natural antioxidants and its application to combat pathological conditions associated with oxidative stress.
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Affiliation(s)
- Alexander Vaiserman
- Laboratory of Epigenetics, D.F. Chebotarev Institute of Gerontology, NAMS, Kyiv, Ukraine
| | - Alexander Koliada
- Laboratory of Epigenetics, D.F. Chebotarev Institute of Gerontology, NAMS, Kyiv, Ukraine
| | - Alina Zayachkivska
- Department of Biochemistry and Biotechnology, Vasyl Stefanyk Precarpathian National University, Ivano-Frankivsk, Ukraine
| | - Oleh Lushchak
- Department of Biochemistry and Biotechnology, Vasyl Stefanyk Precarpathian National University, Ivano-Frankivsk, Ukraine
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Evans LW, Bender A, Burnett L, Godoy L, Shen Y, Staten D, Zhou T, Angermann JE, Ferguson BS. Emodin and emodin-rich rhubarb inhibits histone deacetylase (HDAC) activity and cardiac myocyte hypertrophy. J Nutr Biochem 2020; 79:108339. [PMID: 32007664 DOI: 10.1016/j.jnutbio.2019.108339] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Revised: 11/29/2019] [Accepted: 12/20/2019] [Indexed: 12/25/2022]
Abstract
Pathological cardiac hypertrophy is a classical hallmark of heart failure. At the molecular level, inhibition of histone deacetylase (HDAC) enzymes attenuate pathological cardiac hypertrophy in vitro and in vivo. Emodin is an anthraquinone that has been implicated in cardiac protection. However, it is not known if the cardio-protective actions for emodin are mediated through HDAC-dependent regulation of gene expression. Therefore, we hypothesized that emodin would attenuate pathological cardiac hypertrophy via inhibition of HDACs, and that these actions would be reflected in an emodin-rich food like rhubarb. In this study, we demonstrate that emodin and Turkish rhubarb containing emodin inhibit HDAC activity in vitro, with fast-on, slow-off kinetics. Moreover, we show that emodin increased histone acetylation in cardiomyocytes concomitant to global changes in gene expression; gene expression changes were similar to the well-established pan-HDAC inhibitor trichostatin A (TSA). We additionally present evidence that emodin inhibited phenylephrine (PE) and phorbol myristate acetate (PMA)-induced hypertrophy in neonatal rat ventricular myocytes (NRVMs). Lastly, we demonstrate that the cardioprotective actions of emodin are translated to an angiotensin II (Ang) mouse model of cardiac hypertrophy and fibrosis and are linked to HDAC inhibition. These data suggest that emodin blocked pathological cardiac hypertrophy, in part, by inhibiting HDAC-dependent gene expression changes.
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Affiliation(s)
- Levi W Evans
- Department of Nutrition, University of Nevada, Reno, NV, USA; Environmental Sciences, University of Nevada, Reno, NV, USA
| | - Abigail Bender
- Department of Biochemistry and Molecular Biology, University of Nevada, Reno, NV, USA
| | - Leah Burnett
- Department of Biochemistry and Molecular Biology, University of Nevada, Reno, NV, USA
| | - Luis Godoy
- Department of Nutrition, University of Nevada, Reno, NV, USA
| | - Yi Shen
- Department of Nutrition, University of Nevada, Reno, NV, USA; Department of Biochemistry and Molecular Biology, University of Nevada, Reno, NV, USA
| | - Dante Staten
- Environmental Sciences, University of Nevada, Reno, NV, USA
| | - Tong Zhou
- Department of Biochemistry and Molecular Biology, University of Nevada, Reno, NV, USA
| | | | - Bradley S Ferguson
- Department of Nutrition, University of Nevada, Reno, NV, USA; Environmental Sciences, University of Nevada, Reno, NV, USA; Center of Biomedical Research Excellence for Molecular and Cellular Signal Transduction in the Cardiovascular System, University of Nevada, Reno, NV, USA.
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41
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Lipid Nanoarchitectonics for Natural Products Delivery in Cancer Therapy. SUSTAINABLE AGRICULTURE REVIEWS 2020. [DOI: 10.1007/978-3-030-41842-7_5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Lushchak O, Strilbytska O, Koliada A, Zayachkivska A, Burdyliuk N, Yurkevych I, Storey KB, Vaiserman A. Nanodelivery of phytobioactive compounds for treating aging-associated disorders. GeroScience 2019; 42:117-139. [PMID: 31686375 DOI: 10.1007/s11357-019-00116-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2019] [Accepted: 10/04/2019] [Indexed: 12/15/2022] Open
Abstract
Aging population presents a major challenge for many countries in the world and has made the development of efficient means for healthspan extension a priority task for researchers and clinicians worldwide. Anti-aging properties including antioxidant, anti-inflammatory, anti-tumor, and cardioprotective activities have been reported for various phytobioactive compounds (PBCs) including resveratrol, quercetin, curcumin, catechin, etc. However, the therapeutic potential of orally administered PBCs is limited by their poor stability, bioavailability, and solubility in the gastrointestinal tract. Recently, innovative nanotechnology-based approaches have been developed to improve the bioactivity of PBCs and enhance their potential in preventing and/or treating age-associated disorders, primarily those caused by aging-related chronic inflammation. PBC-loaded nanoparticles designed for oral administration provide many benefits over conventional formulations, including enhanced stability and solubility, prolonged half-life, improved epithelium permeability and bioavailability, enhanced tissue targeting, and minimized side effects. The present review summarizes recent advances in this rapidly developing research area.
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Affiliation(s)
- Oleh Lushchak
- Department of Biochemistry and Biotechnology, Vasyl Stefanyk Precarpathian National University, 57 Shevchenka str., Ivano-Frankivsk, 76018, Ukraine.
| | - Olha Strilbytska
- Department of Biochemistry and Biotechnology, Vasyl Stefanyk Precarpathian National University, 57 Shevchenka str., Ivano-Frankivsk, 76018, Ukraine
| | - Alexander Koliada
- Laboratory of Epigenetics, D.F. Chebotarev Institute of Gerontology, NAMS, 67 Vyshgorodska str., Kyiv, 04114, Ukraine
| | - Alina Zayachkivska
- Department of Biochemistry and Biotechnology, Vasyl Stefanyk Precarpathian National University, 57 Shevchenka str., Ivano-Frankivsk, 76018, Ukraine
| | - Nadia Burdyliuk
- Department of Biochemistry and Biotechnology, Vasyl Stefanyk Precarpathian National University, 57 Shevchenka str., Ivano-Frankivsk, 76018, Ukraine
| | - Ihor Yurkevych
- Department of Biochemistry and Biotechnology, Vasyl Stefanyk Precarpathian National University, 57 Shevchenka str., Ivano-Frankivsk, 76018, Ukraine
| | - Kenneth B Storey
- Department of Biology, Carleton University, 1125 Colonel by Drive, Ottawa, Ontario, K1S 5B6, Canada
| | - Alexander Vaiserman
- Laboratory of Epigenetics, D.F. Chebotarev Institute of Gerontology, NAMS, 67 Vyshgorodska str., Kyiv, 04114, Ukraine.
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43
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Qiu N, Zhao X, Liu Q, Shen B, Liu J, Li X, An L. Inclusion complex of emodin with hydroxypropyl-β-cyclodextrin: Preparation, physicochemical and biological properties. J Mol Liq 2019. [DOI: 10.1016/j.molliq.2019.111151] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
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Azizian-Shermeh O, Valizadeh M, Taherizadeh M, Beigomi M. Phytochemical investigation and phytosynthesis of eco-friendly stable bioactive gold and silver nanoparticles using petal extract of saffron (Crocus sativus L.) and study of their antimicrobial activities. APPLIED NANOSCIENCE 2019. [DOI: 10.1007/s13204-019-01059-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
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45
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Shafique H, Ahad A, Khan W, Want MY, Bhatt PC, Ahmad S, Panda BP, Mujeeb M. Ganoderic acid -loaded solid lipid nanoparticles ameliorate d-galactosamine induced hepatotoxicity in Wistar rats. J Drug Deliv Sci Technol 2019. [DOI: 10.1016/j.jddst.2019.01.005] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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46
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Ji X, Xu W, Cui J, Ma Y, Zhou S. Goat and buffalo milk fat globule membranes exhibit better effects at inducing apoptosis and reduction the viability of HT-29 cells. Sci Rep 2019; 9:2577. [PMID: 30796323 PMCID: PMC6385370 DOI: 10.1038/s41598-019-39546-y] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2017] [Accepted: 01/10/2019] [Indexed: 01/09/2023] Open
Abstract
Bovine milk fat globule membrane (MFGM) has shown many health benefits, however, there has not been much study on non-cattle MFGMs. The purpose of this study was to compare the anti-proliferation effects and investigate the mechanisms of MFGMs from bovine, goat, buffalo, yak and camel milk in HT-29 cells. Results showed that protein content in MFGM of yak milk is the highest among five MFGM. All MFGMs reduced cellular viability which was in agreement with cell morphology and apoptosis. However, the number of cells in S-phase from 24 h to 72 h was increased significantly by treatment with goat, buffalo and bovine MFGMs (100 μg/mL), but not yak and camel. All MFGMs treatment significantly reduced the mitochondrial membrane potential (with an order of goat > buffalo > bovine > camel > yak) and Bcl-2 expression, but increased the expression of both Bax and Caspase-3. Taken together, the results indicate that all MFGMs, especially goat and buffalo MFGMs, showed better effects at inducing apoptosis and reduction the viability of HT-29 cells. The mechanism might be arresting the cell cycle at S phase, depolarization of mitochondrial membrane potential, down-regulation of Bcl-2 expression and increase of Bax and Caspase-3 expression.
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Affiliation(s)
- Xiaoxi Ji
- Department of Food Science and Engineering, School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, 150001, P. R. China
- Key Laboratory of Shandong Provincial Education Department: Past-harvest QC and Multiutilization of Characteristic Agricultural Products, Shandong Agriculture and Food Engineering University, Jinan, Shandong, 250100, P. R. China
| | - Weili Xu
- Department of Food Science and Engineering, School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, 150001, P. R. China
| | - Jie Cui
- Department of Food Science and Engineering, School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, 150001, P. R. China
| | - Ying Ma
- Department of Food Science and Engineering, School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, 150001, P. R. China.
| | - Shaobo Zhou
- School of Life Sciences, Institute of Biomedical and Environmental Science and Technology, University of Bedfordshire, Luton, LU1 3JU, UK.
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Al-Obaidy SSM, Greenway GM, Paunov VN. Dual-functionalised shellac nanocarriers give a super-boost of the antimicrobial action of berberine. NANOSCALE ADVANCES 2019; 1:858-872. [PMID: 36132264 PMCID: PMC9473176 DOI: 10.1039/c8na00121a] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/01/2018] [Accepted: 11/20/2018] [Indexed: 05/06/2023]
Abstract
We have developed highly efficient antimicrobial nanocarriers for berberine (BRB) based on shellac nanoparticles (NPs) which were surface-functionalised with a surface active polymer, Poloxamer 407 (P407), and the cationic surfactant octadecyltrimethylammonium bromide (ODTAB). These shellac nanocarriers were produced in a two-step process which involves: (i) a pH change from aqueous ammonium shellac solution using P407 as a steric stabilizer in the presence of berberine chloride, and (ii) addition of ODTAB to yield shellac nanocarriers of cationic surface. We determined the BRB encapsulation efficiency and release profiles from such nanocarriers. We explored the antimicrobial action of these nanocarriers at different stages of their preparation which allowed us gain better understanding how they work, fine tune their design and reveal the impact of the nanoparticle coatings on to its antimicrobial effect. The antimicrobial action of BRB loaded within such shellac NPs with cationic surface functionality was examined on three different microorganisms, C. reinhardtii, S. cerevisiae and E. coli and compared with the effect of free BRB as well as non-coated BRB-loaded nanocarriers at the same BRB concentrations. We found that the cationic surface coating of the shellac NPs strongly amplified the efficiency of the encapsulated BRB across all tested microorganisms. The effect was attributed to the increased attraction between the ODTAB-coated BRB-loaded NPs and the anionic surface of the cell walls which delivers locally high BRB concentration. This nanotechnological approach could lead to more effective antimicrobial and disinfecting agents, dental formulations for plaque control, wound dressings, antialgal/antibiofouling formulations and antifungal agents.
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Affiliation(s)
- Saba S M Al-Obaidy
- Department of Chemistry and Biochemistry, University of Hull Hull HU67RX UK +44 (0)1482 466410 +44 (0)1482 465660
| | - Gillian M Greenway
- Department of Chemistry and Biochemistry, University of Hull Hull HU67RX UK +44 (0)1482 466410 +44 (0)1482 465660
| | - Vesselin N Paunov
- Department of Chemistry and Biochemistry, University of Hull Hull HU67RX UK +44 (0)1482 466410 +44 (0)1482 465660
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48
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Tween 80-modified hyaluronic acid-ss-curcumin micelles for targeting glioma: Synthesis, characterization and their in vitro evaluation. Int J Biol Macromol 2018; 120:2579-2588. [DOI: 10.1016/j.ijbiomac.2018.09.034] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2018] [Revised: 08/29/2018] [Accepted: 09/05/2018] [Indexed: 01/19/2023]
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49
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Zhai Q, Li H, Song Y, Wu R, Tang C, Ma X, Liu Z, Peng J, Zhang J, Tang Z. Preparation and Optimization Lipid Nanocapsules to Enhance the Antitumor Efficacy of Cisplatin in Hepatocellular Carcinoma HepG2 Cells. AAPS PharmSciTech 2018; 19:2048-2057. [PMID: 29679292 DOI: 10.1208/s12249-018-1011-6] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2017] [Accepted: 04/03/2018] [Indexed: 02/06/2023] Open
Abstract
This work aimed to develop and optimize several lipid nanocapsule formulations (LNCs) to encapsulate cisplatin (CDDP) for treatment of hepatocellular carcinoma. By comparing the effect of oil/surfactant ratio, lecithin content, and oil/surfactant type on LNC characteristics, two LNCs were selected as optimal formulations: HS15-LNC (Solutol HS 15/MCT/lecithin, 54.5:42.5:3%, w/w) and EL-LNC (Cremophor EL/MCT/lecithin, 54.5:42.5:3%, w/w). Both LNCs could effectively encapsulate CDDP with the encapsulation efficiency of 73.48 and 78.84%. In vitro release study showed that both LNCs could sustain the release CDDP. Moreover, cellular uptake study showed that C6-labeled LNCs could be effectively internalized by HepG2 cells. Cellular cytotoxicity study revealed that both LNCs showed negligible cellular toxicity when their concentrations were below 313 μg/mL. Importantly, CDDP-loaded LNCs exhibited much stronger cell killing potency than free CDDP, with the IC50 values decreased from 17.93 to 3.53 and 5.16 μM after 72-h incubation. In addition, flow cytometric analysis showed that the percentage of apoptotic cells was significantly increased after treatment with LNCs. Therefore, the prepared LNC formulations exhibited promising anti-hepatocarcinoma effect, which could be beneficial to hepatocellular carcinoma therapy.
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Affiliation(s)
- Qingqing Zhai
- College of Pharmacy, Dalian Medical University, Dalian, 116044, People's Republic of China
| | - Hailong Li
- College of Pharmacy, Dalian Medical University, Dalian, 116044, People's Republic of China
| | - Yanlin Song
- College of Pharmacy, Dalian Medical University, Dalian, 116044, People's Republic of China
| | - Ruijiao Wu
- College of Pharmacy, Dalian Medical University, Dalian, 116044, People's Republic of China
| | - Chuanfang Tang
- College of Pharmacy, Dalian Medical University, Dalian, 116044, People's Republic of China
| | - Xiaodong Ma
- College of Pharmacy, Dalian Medical University, Dalian, 116044, People's Republic of China
| | - Zhihao Liu
- College of Pharmacy, Dalian Medical University, Dalian, 116044, People's Republic of China
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, People's Republic of China
| | - Jinyong Peng
- College of Pharmacy, Dalian Medical University, Dalian, 116044, People's Republic of China
| | - Jianbin Zhang
- College of Pharmacy, Dalian Medical University, Dalian, 116044, People's Republic of China.
| | - Zeyao Tang
- College of Pharmacy, Dalian Medical University, Dalian, 116044, People's Republic of China.
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Drug Delivery System for Emodin Based on Mesoporous Silica SBA-15. NANOMATERIALS 2018; 8:nano8050322. [PMID: 29757198 PMCID: PMC5977336 DOI: 10.3390/nano8050322] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/07/2018] [Revised: 05/04/2018] [Accepted: 05/07/2018] [Indexed: 12/13/2022]
Abstract
In this study mesoporous silica SBA-15 was evaluated as a vehicle for the transport of cytotoxic natural product emodin (EO). SBA-15 was loaded with different quantities of EO (SBA-15|EO1–SBA-15|EO5: 8–36%) and characterized by traditional methods. Several parameters (stabilities) and the in vitro behavior on tumor cell lines (melanoma A375, B16 and B16F10) were investigated. SBA-15 suppresses EO release in extremely acidic milieu, pointing out that EO will not be discharged in the stomach. Furthermore, SBA-15 protects EO from photodecomposition. In vitro studies showed a dose dependent decrease of cellular viability which is directly correlated with an increasing amount of EO in SBA-15 for up to 27% of EO, while a constant activity for 32% and 36% of EO in SBA-15 was observed. Additionally, SBA-15 loaded with EO (SBA-15|EO3) does not disturb viability of peritoneal macrophages. SBA-15|EO3 causes inhibition of tumor cell proliferation and triggers apoptosis, connected with caspase activation, upregulation of Bax, as well as Bcl-2 and Bim downregulation along with amplification of poly-(ADP-ribose)-polymerase (PARP) cleavage fragment. Thus, the mesoporous SBA-15 is a promising carrier of the water-insoluble drug emodin.
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