|
1
|
Panchal K, Patel Y, Jani H, Dalal M, Chidrawar VR, Datta D, Mohite P, Puri A, Ranch K, Singh S. Indomethacin-incorporated microemulsion-laden contact lenses for improved ocular drug delivery and therapeutic efficacy. RSC Adv 2025; 15:16110-16124. [PMID: 40370851 PMCID: PMC12077302 DOI: 10.1039/d5ra01046b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2025] [Accepted: 04/21/2025] [Indexed: 05/16/2025] Open
Abstract
Conventional eye drops are associated with several limitations, including rapid drug clearance and low bioavailability, with only about 5% of the administered drug reaching the cornea to demonstrate therapeutic efficacy. Thus, to address these challenges, indomethacin (IND)-loaded microemulsion (Me)-embedded soft contact lenses (CLs) were developed to improve ocular drug delivery. The D-optimal mixture design was employed to optimize the composition of the Me formulation. Independent variables included Capmul MCM (oil phase), S mix (Tween 80/isopropyl alcohol), and water, while dependent variables were the globule size, transmittance (%), and drug release profile. The optimized Me exhibited a globule diameter of 45.69 ± 1.85 nm and a transmittance of 99.4% ± 1.59%. The globule dispersion index (PDI) was 0.33 ± 0.06, and the zeta potential (ZP) was 0.657 ± 0.012 mV. Soft CLs were developed using free radical polymerization and fortified with the Me loaded with the drug through direct loading and soaking techniques. Direct loading achieved a swelling percentage of 96.37% ± 1.8% and a transmittance of 96.5% ± 0.3%, while soaking resulted in 97.57% ± 1.4% swelling and 97.3% ± 1.3% transmittance. A drug content of 19.76 ± 0.23 μg per lenses for direct loading and 29.8 ± 0.2 μg per lenses for soaking demonstrated that the efficacy of the soaking technique was higher than that of direct loading. Moreover, drug release studies showed that the Me-laden lenses prepared using the direct loading technique released 44.00% ± 0.53% to 53.00% ± 0.59% of the drug within the first 6 h, while the lenses prepared via soaking released 62.58% ± 1.56% to 97.64% ± 1.52% of the drug within the first 6 h, followed by regulated drug release for up to 28 h, maintaining clarity and drug loading. Ocular irritancy test results indicated negligible irritation, suggesting that the Me-laden lenses are a safe and effective platform to manage ocular inflammation with the controlled delivery of IND.
Collapse
Affiliation(s)
- Kashvi Panchal
- Department of Pharmaceutics and Pharmaceutical Technology, L. M. College of Pharmacy Ahmedabad Gujarat 380009 India
| | - Yashkumar Patel
- Department of Pharmaceutics and Pharmaceutical Technology, L. M. College of Pharmacy Ahmedabad Gujarat 380009 India
| | - Harshilkumar Jani
- Department of Pharmaceutics and Pharmaceutical Technology, L. M. College of Pharmacy Ahmedabad Gujarat 380009 India
| | - Mittal Dalal
- Department of Pharmacology, L. M. College of Pharmacy Ahmedabad Gujarat 380009 India
| | - Vijay R Chidrawar
- School of Pharmacy and Technology Management, SVKM's Narsee Monjee Institute of Management Studies (NMIMS), Deemed-to-University Green Industrial Park, TSIIC, Jadcherla Hyderabad 509301 India
| | - Deepanjan Datta
- Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education Manipal Karnataka 576104 India
| | - Popat Mohite
- AETs St. John Institute of Pharmacy and Research Palghar Maharashtra 401404 India
| | - Abhijeet Puri
- AETs St. John Institute of Pharmacy and Research Palghar Maharashtra 401404 India
| | - Ketan Ranch
- Department of Pharmaceutics and Pharmaceutical Technology, L. M. College of Pharmacy Ahmedabad Gujarat 380009 India
| | - Sudarshan Singh
- Office of Research Administration, Chiang Mai University Chiang Mai 50200 Thailand
- Faculty of Pharmacy, Chiang Mai University Chiang Mai 50200 Thailand
| |
Collapse
|
|
2
|
Sarkar T, Gogoi NR, Jana BK, Mazumder B. Formulation Advances in Posterior Segment Ocular Drug Delivery. J Ocul Pharmacol Ther 2025; 41:101-130. [PMID: 39842469 DOI: 10.1089/jop.2024.0153] [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] [Indexed: 01/24/2025] Open
Abstract
Posterior segment ocular diseases, such as diabetic retinopathy, age-related macular degeneration, and retinal vein occlusion, are leading causes of vision impairment and blindness worldwide. Effective management of these conditions remains a formidable challenge due to the unique anatomical and physiological barriers of the eye, including the blood-retinal barrier and rapid drug clearance mechanisms. To address these hurdles, nanostructured drug delivery systems are proposed to overcome ocular barriers, target the retina, and enhance permeation while ensuring controlled release. Traditional therapeutic approaches, such as intravitreal injections, pose significant drawbacks, including patient discomfort, poor compliance, and potential complications. Therefore, understanding the physiology and clearance mechanism of eye could aid in the design of novel formulations that could be noninvasive and deliver drugs to reach the target site is pivotal for effective treatment strategies. This review focuses on recent advances in formulation strategies for posterior segment ocular drug delivery, highlighting their potential to overcome these limitations. Furthermore, the potential of nanocarrier systems such as in-situ gel, niosomes, hydrogels, dendrimers, liposomes, nanoparticles, and nanoemulsions for drug delivery more effectively and selectively is explored, and supplemented with illustrative examples, figures, and tables. This review aims to provide insights into the current state of posterior segment drug delivery, emphasizing the need for interdisciplinary approaches to develop patient-centric, minimally invasive, and effective therapeutic solutions.
Collapse
Affiliation(s)
- Tumpa Sarkar
- Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh, India
| | - Niva Rani Gogoi
- Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh, India
| | - Bani Kumar Jana
- Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh, India
| | - Bhaskar Mazumder
- Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh, India
| |
Collapse
|
|
3
|
Bernardi E, Shah N, Ferro Desideri L, Potic J, Roth J, Anguita R. Cystoid Macular Edema Following Rhegmatogenous Retinal Detachment Repair Surgery: Incidence, Pathogenesis, Risk Factors and Treatment. Clin Ophthalmol 2025; 19:629-639. [PMID: 40007877 PMCID: PMC11853832 DOI: 10.2147/opth.s489859] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Accepted: 12/20/2024] [Indexed: 02/27/2025] Open
Abstract
Purpose To review the incidence, risk factors, and treatments for cystoid macular edema (CME) following rhegmatogenous retinal detachment (RRD) repair surgery. Methods A comprehensive literature search was conducted across multiple databases. Relevant studies published within the last 20 years were selected and reviewed. Results The incidence of CME following RRD repair ranges from 6% to 36%, with higher rates associated with silicone oil tamponade. Key risk factors include recurrent RRD, pre-existing proliferative vitreoretinopathy, older age, and post-RRD cataract surgery. Treatment options primarily focus on anti-inflammatory approaches, with topical NSAIDs and corticosteroids as first-line treatments. For persistent cases, intravitreal corticosteroid injections, particularly dexamethasone implants, have shown potential. Conclusion CME remains a significant complication following RRD repair, impacting visual recovery. While various treatment options exist, management of persistent CME remains challenging. Better understanding of the underlying mechanisms of CME is required to develop more effective treatment strategies, particularly for cases resistant to current therapies.
Collapse
Affiliation(s)
- Enrico Bernardi
- Department of Ophthalmology, Inselspital, Bern University Hospital, University of Bern, Bern, CH-3010, Switzerland
| | - Neil Shah
- Moorfields Eye Hospital NHS Foundation Trust, London, UK
| | - Lorenzo Ferro Desideri
- Department of Ophthalmology, Inselspital, Bern University Hospital, University of Bern, Bern, CH-3010, Switzerland
- Bern Photographic Reading Center, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Jelena Potic
- Department of Ophthalmology, University of Lausanne, Jules-Gonin Eye Hospital, Fondation Asile des Aveugles, Lausanne, Switzerland
| | - Janice Roth
- Department of Ophthalmology, Inselspital, Bern University Hospital, University of Bern, Bern, CH-3010, Switzerland
- Moorfields Eye Hospital NHS Foundation Trust, London, UK
| | - Rodrigo Anguita
- Department of Ophthalmology, Inselspital, Bern University Hospital, University of Bern, Bern, CH-3010, Switzerland
- Moorfields Eye Hospital NHS Foundation Trust, London, UK
| |
Collapse
|
|
4
|
Moritake K, Tsuchida T, Koga R, Hasegawa K, Kuwashima W, Kataoka H, Goto S, Terada H. Equilibrium of monomers, dimers, and polymeric aggregates in the α-aryl-propionic acid-type analgesics naproxen, ketoprofen, and ibuprofen: Comparative study with oxicam-type meloxicam and piroxicam. Int J Pharm 2025; 670:125167. [PMID: 39756600 DOI: 10.1016/j.ijpharm.2025.125167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Revised: 12/11/2024] [Accepted: 01/02/2025] [Indexed: 01/07/2025]
Abstract
Hydrophobicity is associated with drug transport across membranes and is expressed as the partition coefficient log P for neutral drugs and the distribution coefficient log D for acidic and basic drugs. The log P and log D predictions are deductively (or with artificial intelligence) estimated as the sum of the partial contributions of the scaffold and substituents of a single molecule and are used widely and affirmatively. However, their predictions have not always been comprehensively accurate beyond scaffold differences. For α-aryl propionic acid and oxicam-type analgesics, the pH profiles and methanol contents dependence on hydrophobicity were examined using reversed-phase HPLC, the conventional flask-shaking method. UV spectroscopy and singular value decomposition (SVD) were used to determine the acid dissociation constants. The dehydration of organic solutes in aqueous solutions by methanol rearranged their dispersion states. Therefore, their fluorescent excitation spectra switched dependently on the fluorophore's concentration, suggesting that α-aryl propionic acid-type analgesics reach equilibrium in monomers, dimers, and polymeric aggregations but the oxicam-type ones cannot achieve dimerization. Their dissolution behaviors are dominated by phenomenological processes, generating a type of dissipative structure that is adaptive to the features of individual solutes. The results of this study suggest that the apparent hydrophobicity of organic solutes is reflected in the dissolved state.
Collapse
Affiliation(s)
- Kota Moritake
- Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan
| | - Tomohiro Tsuchida
- Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan
| | - Ryotaro Koga
- Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan
| | - Kanji Hasegawa
- Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan
| | - Wataru Kuwashima
- Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan
| | - Hikaru Kataoka
- Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan
| | - Satoru Goto
- Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
| | - Hiroshi Terada
- Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan
| |
Collapse
|
|
5
|
Qi Q, Su D, Zhuang S, Yao S, Heindl LM, Fan X, Lin M, Li J, Pang Y. Progress in Nanotechnology for Treating Ocular Surface Chemical Injuries: Reflecting on Advances in Ophthalmology. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2025; 12:e2407340. [PMID: 39755928 PMCID: PMC11809354 DOI: 10.1002/advs.202407340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 11/26/2024] [Indexed: 01/06/2025]
Abstract
Ocular surface chemical injuries often result in permanent visual impairment and necessitate complex, long-term treatments. Immediate and extensive irrigation serves as the first-line intervention, followed by various therapeutic protocols applied throughout different stages of the condition. To optimize outcomes, conventional regimens increasingly incorporate biological agents and surgical techniques. In recent years, nanotechnology has made significant strides, revolutionizing the management of ocular surface chemical injuries by enabling sustained drug release, enhancing treatment efficacy, and minimizing side effects. This review provides a comprehensive analysis of the etiology, epidemiology, classification, and conventional therapies for ocular chemical burns, with a special focus on nanotechnology-based drug delivery systems in managing ocular surface chemical injuries. Twelve categories of nanocarrier platforms are examined, including liposomes, nanoemulsions, nanomicelles, nanowafers, nanostructured lipid carriers, nanoparticles, hydrogels, dendrimers, nanocomplexes, nanofibers, nanozymes, and nanocomposite materials, highlighting their advantages in targeted delivery, biocompatibility, and improved healing efficacy. Additionally, current challenges and limitations in the field are discussed and the future potential of nanotechnology in treating ocular diseases is explored. This review presents the most extensive examination of this topic to date, aiming to link recent advancements with broader therapeutic strategies.
Collapse
Affiliation(s)
- Qiaoran Qi
- Department of OphthalmologyNinth People's HospitalShanghai Jiao Tong University School of MedicineShanghai200011China
- Shanghai Key Laboratory of Orbital Diseases and Ocular OncologyCenter for Basic Medical Research and Innovation in Visual System DiseasesMinistry of EducationShanghai200011China
| | - Dai Su
- Department of OphthalmologyNinth People's HospitalShanghai Jiao Tong University School of MedicineShanghai200011China
- Shanghai Key Laboratory of Orbital Diseases and Ocular OncologyCenter for Basic Medical Research and Innovation in Visual System DiseasesMinistry of EducationShanghai200011China
| | - Shuqin Zhuang
- Department of OphthalmologyNinth People's HospitalShanghai Jiao Tong University School of MedicineShanghai200011China
- Shanghai Key Laboratory of Orbital Diseases and Ocular OncologyCenter for Basic Medical Research and Innovation in Visual System DiseasesMinistry of EducationShanghai200011China
| | - Sunyuan Yao
- Department of OphthalmologyNinth People's HospitalShanghai Jiao Tong University School of MedicineShanghai200011China
- Shanghai Key Laboratory of Orbital Diseases and Ocular OncologyCenter for Basic Medical Research and Innovation in Visual System DiseasesMinistry of EducationShanghai200011China
| | - Ludwig M. Heindl
- Department of OphthalmologyFaculty of Medicine and University Hospital CologneUniversity of Cologne50937CologneGermany
- Center for Integrated Oncology (CIO)Aachen‐Bonn‐Cologne‐DuesseldorfCologneGermany
| | - Xianqun Fan
- Department of OphthalmologyNinth People's HospitalShanghai Jiao Tong University School of MedicineShanghai200011China
- Shanghai Key Laboratory of Orbital Diseases and Ocular OncologyCenter for Basic Medical Research and Innovation in Visual System DiseasesMinistry of EducationShanghai200011China
| | - Ming Lin
- Department of OphthalmologyNinth People's HospitalShanghai Jiao Tong University School of MedicineShanghai200011China
- Shanghai Key Laboratory of Orbital Diseases and Ocular OncologyCenter for Basic Medical Research and Innovation in Visual System DiseasesMinistry of EducationShanghai200011China
| | - Jin Li
- Department of OphthalmologyNinth People's HospitalShanghai Jiao Tong University School of MedicineShanghai200011China
- Shanghai Key Laboratory of Orbital Diseases and Ocular OncologyCenter for Basic Medical Research and Innovation in Visual System DiseasesMinistry of EducationShanghai200011China
| | - Yan Pang
- Department of OphthalmologyNinth People's HospitalShanghai Jiao Tong University School of MedicineShanghai200011China
- Shanghai Key Laboratory of Orbital Diseases and Ocular OncologyCenter for Basic Medical Research and Innovation in Visual System DiseasesMinistry of EducationShanghai200011China
- Shanghai Frontiers Science Center of Drug Target Identification and DeliverySchool of Pharmaceutical SciencesShanghai Jiao Tong UniversityShanghai200240China
| |
Collapse
|
|
6
|
Yang L, Li X, Zhang Y, Tian J, Ling G, Zhang P. Construction of a thermosensitive gel based on hydroxypropyl-β-cyclodextrin/meloxicam inclusion complexes for improving meloxicam solubility and prolonging drug retention time in the cornea. Drug Deliv Transl Res 2025:10.1007/s13346-025-01797-w. [PMID: 39849286 DOI: 10.1007/s13346-025-01797-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/14/2025] [Indexed: 01/25/2025]
Abstract
The eyes are easily stimulated by external factors, which can cause inflammation. Anti-inflammatory drugs are usually used to inhibit the production of inflammatory factors. Many nonsteroidal anti-inflammatory drugs have been used for the eye, but due to the poor solubility of meloxicam, there are currently no marketed meloxicam preparations for the treatment of eye diseases. This article uses hydroxypropyl-β-CD (HP-β-CD) to encapsulate meloxicam and combined with thermosensitive gel to prepare an HP-β-CD/meloxicam inclusion complex eye thermosensitive gel, which can improved the water solubility of meloxicam and extend the retention time of the drug in the cornea, and achieve the goal of slow release through continuous dissolution. It not only has the advantages of convenient administration and accurate dosage of eye drops, but also overcomes the disadvantage of easy loss of eye drops, showing the advantages of long retention time and fewer administration times, and provides a basis for the development of other dosage forms of meloxicam.
Collapse
Affiliation(s)
- Lvyao Yang
- Wuya College of Innovation, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang, 110016, China
| | - Xiu'e Li
- Wuya College of Innovation, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang, 110016, China
- CSPC Pharmaceutical Group Zhongqi Pharmacy (Shijiazhuang) Co., Ltd., Shiiazhuang, China
| | - Yuanke Zhang
- Wuya College of Innovation, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang, 110016, China
| | - Jingjing Tian
- Wuya College of Innovation, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang, 110016, China
| | - Guixia Ling
- Wuya College of Innovation, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang, 110016, China
| | - Peng Zhang
- Wuya College of Innovation, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang, 110016, China.
| |
Collapse
|
|
7
|
Bisen AC, Dubey A, Agrawal S, Biswas A, Rawat KS, Srivastava S, Bhatta RS. Recent updates on ocular disease management with ophthalmic ointments. Ther Deliv 2024; 15:463-480. [PMID: 38888757 DOI: 10.1080/20415990.2024.2346047] [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: 10/31/2023] [Accepted: 04/18/2024] [Indexed: 06/20/2024] Open
Abstract
Ophthalmic diseases can result in permanent vision loss and blindness. Convenient topical and systemic treatments are preferred to address these sight-threatening conditions. However, the unique anatomy of the eye presents challenges for drug delivery. Various ophthalmic ointment formulations have been developed to enhance bioavailability in the eye to prolong residence time and improve corneal permeability. This article explores a wide range of ocular diseases affecting individuals globally and how ointments are used to manage them. From eye to ocular barriers, this review focuses on published scientific research and formulation strategies for severe ocular complications using conventional topical ointments. Additionally, it delves through patented technologies and marketed formulations supporting the use of ointments in ocular drug delivery.
Collapse
Affiliation(s)
- Amol Chhatrapati Bisen
- Pharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute, Lucknow, 226031, Uttar Pradesh, India
- Academy of Scientific & Innovative Research (AcSIR), Ghaziabad, 201002, Uttar Pradesh, India
- Sophisticated Analytical Instrument Facility and Research, CSIR-Central Drug Research Institute, Lucknow, 226031, Uttar Pradesh, India
| | - Ayush Dubey
- Pharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute, Lucknow, 226031, Uttar Pradesh, India
- School of Pharmaceutical Sciences, CSJM University, Kanpur, 208024, Uttar Pradesh, India
| | - Sristi Agrawal
- Pharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute, Lucknow, 226031, Uttar Pradesh, India
- Academy of Scientific & Innovative Research (AcSIR), Ghaziabad, 201002, Uttar Pradesh, India
| | - Arpon Biswas
- Pharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute, Lucknow, 226031, Uttar Pradesh, India
| | - Kundan Singh Rawat
- Prof. Rajendra Singh Nanoscience & Chemistry D.S.B. Campus, Kumaun University, Nainital, 263001, Uttarakhand, India
| | - Saurabh Srivastava
- Pharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute, Lucknow, 226031, Uttar Pradesh, India
- School of Pharmaceutical Sciences, CSJM University, Kanpur, 208024, Uttar Pradesh, India
| | - Rabi Sankar Bhatta
- Pharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute, Lucknow, 226031, Uttar Pradesh, India
- Academy of Scientific & Innovative Research (AcSIR), Ghaziabad, 201002, Uttar Pradesh, India
| |
Collapse
|
|
8
|
Vallejo R, Quinteros D, Gutiérrez J, Martínez S, Rodríguez Rojo S, Ignacio Tártara L, Palma S, Javier Arias F. Acetazolamide encapsulation in elastin like recombinamers using a supercritical antisolvent (SAS) process for glaucoma treatment. Int J Pharm 2024; 657:124098. [PMID: 38621614 DOI: 10.1016/j.ijpharm.2024.124098] [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: 02/28/2024] [Revised: 04/02/2024] [Accepted: 04/05/2024] [Indexed: 04/17/2024]
Abstract
Glaucoma, the second most common cause of blindness worldwide, requires the development of new and effective treatments. This study introduces a novel controlled-release system utilizing elastin-like recombinamers (ELR) and the Supercritical Antisolvent (SAS) technique with supercritical CO2. Acetazolamide (AZM), a class IV drug with limited solubility and permeability, is successfully encapsulated in an amphiphilic ELR at three different ELR:AZM ratios, yielding up to 62 %. Scanning electron microscopy (SEM) reveals spherical microparticles that disintegrate into monodisperse nanoparticles measuring approximately 42 nm under physiological conditions. The nanoparticles, as observed via Transmission Electron Microscopy (TEM) and Atomic Force Microscopy (AFM), do not exhibit aggregates, a fact confirmed by the zeta potential displaying a value of -33 mV over a period of 30 days. Transcorneal permeation tests demonstrate a 10 % higher permeation level compared to the control solution, which increases to 30 % after 2 h. Ocular irritation tests demonstrate no adverse effects or damage. Intraocular pressure (IOP) tests conducted on hypertensive rabbits indicate greater effectiveness for all three analyzed formulations, suggesting enhanced drug bioavailability during treatment. Consequently, the combination of recombinant biopolymers and high-pressure techniques represents a promising approach for advancing glaucoma therapy, emphasizing its potential clinical significance.
Collapse
Affiliation(s)
- Reinaldo Vallejo
- Smart Devices for Nano Medicine Group, Unidad Excelencia Instituto de BioMedicina y Genética Molecular (IBGM) de Valladolid, University of Valladolid and CSIC, Valladolid, Spain; BioEcoUVa, Research Institute on Bioeconomy, High Pressure Process Group, University of Valladolid, Department of Chemical Engineering and Environmental Technology, Escuela de Ingenierías Industriales, Sede Mergelina, 47011 Valladolid, Spain
| | - Daniela Quinteros
- Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), CONICET and Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, 5000 Córdoba, Argentina.
| | - Javier Gutiérrez
- Smart Devices for Nano Medicine Group, Unidad Excelencia Instituto de BioMedicina y Genética Molecular (IBGM) de Valladolid, University of Valladolid and CSIC, Valladolid, Spain
| | - Sofía Martínez
- Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), CONICET and Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, 5000 Córdoba, Argentina
| | - Soraya Rodríguez Rojo
- BioEcoUVa, Research Institute on Bioeconomy, High Pressure Process Group, University of Valladolid, Department of Chemical Engineering and Environmental Technology, Escuela de Ingenierías Industriales, Sede Mergelina, 47011 Valladolid, Spain
| | - Luis Ignacio Tártara
- Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), CONICET and Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, 5000 Córdoba, Argentina
| | - Santiago Palma
- Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), CONICET and Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, 5000 Córdoba, Argentina
| | - Francisco Javier Arias
- Smart Devices for Nano Medicine Group, Unidad Excelencia Instituto de BioMedicina y Genética Molecular (IBGM) de Valladolid, University of Valladolid and CSIC, Valladolid, Spain.
| |
Collapse
|
|
9
|
Kim E, Kwon HJ, Park SW, Byon I. Effect of topical bromfenac on intraretinal cystoid lesion in simultaneous cataract and idiopathic epiretinal membrane surgery. BMC Ophthalmol 2024; 24:120. [PMID: 38491368 PMCID: PMC10943811 DOI: 10.1186/s12886-024-03380-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Accepted: 03/04/2024] [Indexed: 03/18/2024] Open
Abstract
PURPOSE To investigate the effect of topical nonsteroidal anti-inflammatory drugs (NSAIDs,) bromfenac on the intraretinal cystic lesions (IRC) when performing simultaneous cataract and idiopathic epiretinal membrane (iERM) surgery. METHODS This study included patients with iERM who had been followed up for 6 months after vitrectomy, membrane removal, and concurrent cataract surgery. Eyes were treated with topical bromfenac or not. The baseline fluorescein angiography (FA) was obtained to assess the microvascular leakage (ML). Structural changes of macula, including IRC and central macular thickness (CMT) were assessed using optical coherence tomography (OCT). The main outcome measures were changes in IRCs and best-corrected visual acuity (BCVA) regarding FA findings. RESULTS One hundred eighteen eyes were included. IRC and ML were observed in 51 eyes (43.2%) and 63 eyes (53.4%), respectively. The IRC did not show any association with the ML. Of total, 29 eyes (24.6%) were treated with topical bromfenac (Group A). Compared to Group B, topical bromfenac did not show beneficial effects in aspect of preventions for the newly developed IRC and treatment for pre-existed IRC. Whether the ML existed or not, topical bromfenac did not show any different effect on the changes in BCVA and IRC. CONCLUSION When performing simultaneous cataract and ERM surgery, topical NSAIDs, bromfenac did not show beneficial effects on the preventions and treatment of IRC in both eyes with and without the ML.
Collapse
Affiliation(s)
- EunAh Kim
- Department of Ophthalmology, Inje University Haeundae Paik Hospital, Busan, South Korea
| | - Han Jo Kwon
- Department of Ophthalmology, Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea
| | - Sung Who Park
- Department of Ophthalmology, Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea
- Pusan National University School of Medicine, Yangsan, South Korea
| | - Iksoo Byon
- Department of Ophthalmology, Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea.
- Pusan National University School of Medicine, Yangsan, South Korea.
| |
Collapse
|
|
10
|
Paganini V, Chetoni P, Di Gangi M, Monti D, Tampucci S, Burgalassi S. Nanomicellar eye drops: a review of recent advances. Expert Opin Drug Deliv 2024; 21:381-397. [PMID: 38396342 DOI: 10.1080/17425247.2024.2323208] [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: 12/26/2023] [Accepted: 02/21/2024] [Indexed: 02/25/2024]
Abstract
INTRODUCTION Research on nanotechnology in medicine has also involved the ocular field and nanomicelles are among the applications developed. This approach is used to increase both the water solubility of hydrophobic drugs and their penetration/permeation within/through the ocular tissues since nanomicelles are able to encapsulate insoluble drug into their core and their small size allows them to penetrate and/or diffuse through the aqueous pores of ocular tissues. AREAS COVERED The present review reports the most significant and recent literature on the use of nanomicelles, made up of both surfactants and amphiphilic polymers, to overcome limitations imposed by the physiology of the eye in achieving a high bioavailability of drugs intended for the therapeutic areas of greatest commercial interest: dry eye, inflammation, and glaucoma. EXPERT OPINION The results of the numerous studies in this field are encouraging and demonstrate that nanomicelles may be the answer to some of the challenges of ocular therapy. In the future, new molecules self-assembling into micelles will be able to meet the regulatory requirements for marketing authorization for their use in ophthalmic formulations.
Collapse
Affiliation(s)
| | - Patrizia Chetoni
- Department of Pharmacy, University of Pisa, Pisa, Italy
- Inter-University Center for the Promotion of the Rs Principles in Teaching & Research (CentroR), Pisa, Italy
| | | | - Daniela Monti
- Department of Pharmacy, University of Pisa, Pisa, Italy
- Inter-University Center for the Promotion of the Rs Principles in Teaching & Research (CentroR), Pisa, Italy
| | - Silvia Tampucci
- Department of Pharmacy, University of Pisa, Pisa, Italy
- Inter-University Center for the Promotion of the Rs Principles in Teaching & Research (CentroR), Pisa, Italy
| | - Susi Burgalassi
- Department of Pharmacy, University of Pisa, Pisa, Italy
- Inter-University Center for the Promotion of the Rs Principles in Teaching & Research (CentroR), Pisa, Italy
| |
Collapse
|
|
11
|
Fadaei MS, Fadaei MR, Kheirieh AE, Rahmanian-Devin P, Dabbaghi MM, Nazari Tavallaei K, Shafaghi A, Hatami H, Baradaran Rahimi V, Nokhodchi A, Askari VR. Niosome as a promising tool for increasing the effectiveness of anti-inflammatory compounds. EXCLI JOURNAL 2024; 23:212-263. [PMID: 38487088 PMCID: PMC10938253 DOI: 10.17179/excli2023-6868] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Accepted: 01/16/2024] [Indexed: 03/17/2024]
Abstract
Niosomes are drug delivery systems with widespread applications in pharmaceutical research and the cosmetic industry. Niosomes are vesicles of one or more bilayers made of non-ionic surfactants, cholesterol, and charge inducers. Because of their bilayer characteristics, similar to liposomes, niosomes can be loaded with lipophilic and hydrophilic cargos. Therefore, they are more stable and cheaper in preparation than liposomes. They can be classified into four categories according to their sizes and structures, namely small unilamellar vesicles (SUVs), large unilamellar vesicles (LUVs,), multilamellar vesicles (MLVs), and multivesicular vesicles (MVVs). There are many methods for niosome preparation, such as thin-film hydration, solvent injection, and heating method. The current study focuses on the preparation methods and pharmacological effects of niosomes loaded with natural and chemical anti-inflammatory compounds in kinds of literature during the past decade. We found that most research was carried out to load anti-inflammatory agents like non-steroidal anti-inflammatory drugs (NSAIDs) into niosome vesicles. The studies revealed that niosomes could improve anti-inflammatory agents' physicochemical properties, including solubility, cellular uptake, stability, encapsulation, drug release and liberation, efficiency, and oral bioavailability or topical absorption. See also the graphical abstract(Fig. 1).
Collapse
Affiliation(s)
- Mohammad Saleh Fadaei
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammad Reza Fadaei
- Department of Pharmaceutics, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amir Emad Kheirieh
- Department of Pharmaceutics, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Pouria Rahmanian-Devin
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Pharmaceutics, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | | | - Abouzar Shafaghi
- Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hooman Hatami
- Department of Pharmaceutics, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Vafa Baradaran Rahimi
- Department of Cardiovascular Diseases, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Ali Nokhodchi
- Lupin Pharmaceutical Research Center, 4006 NW 124th Ave., Coral Springs, Florida, FL 33065, USA
- Pharmaceutics Research Laboratory, School of Life Sciences, University of Sussex, Brighton BN1 9QJ, UK
| | - Vahid Reza Askari
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| |
Collapse
|
|
12
|
Omran S, Elnaggar YSR, Abdallah OY. Controlled release, chitosan-tethered luteolin phytocubosomes; Formulation optimization to in-vivo antiglaucoma and anti-inflammatory ocular evaluation. Int J Biol Macromol 2024; 254:127930. [PMID: 37944733 DOI: 10.1016/j.ijbiomac.2023.127930] [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: 08/17/2023] [Revised: 10/31/2023] [Accepted: 11/05/2023] [Indexed: 11/12/2023]
Abstract
A chitosan-coated luteolin-loaded phytocubosomal system was prepared to improve the pharmacodynamic performance of luteolin in the treatment of glaucoma and ocular inflammation after topical ocular administration. Luteolin, a potent anti-oxidant herbal drug with poor aqueous solubility, was complexed with phospholipid. The prepared phytocubosomes were coated with chitosan, producing homogenously distributed nanosized particles (258 ± 9.05 nm) with a positive charge (+49 ± 6.09 mV), improved EE% (96 %), and increased concentration of encapsulated drug to 288 μg/ml. Polarized light microscopy revealed a cubic phase. Chitosan-coated phytocubosomes showed a sustained drug release profile (38 % over 24 h) and improved anti-oxidant activity (IC50 of 32 μg/ml). Ex vivo transcorneal permeation was higher by 3.60 folds compared to luteolin suspension. Irritancy tests confirmed their safety in ocular tissues after single and multiple administrations. The pharmacodynamic studies on glaucomatous rabbit eyes demonstrated 6.46-, 3.88-, and 1.89-fold reductions in IOP of chitosan-coated phytocubosomes compared to luteolin suspension, cubosomes, and phytocubosomes, respectively. Pharmacodynamic anti-inflammatory studies revealed faster recovery capabilities of chitosan-coated phytocubosomes over other formulations. Thus, chitosan-coated phytocubosomes could be a promising ocular hybrid system for delivering herbal lipophilic drugs such as luteolin.
Collapse
Affiliation(s)
- Sarah Omran
- Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Egypt
| | - Yosra S R Elnaggar
- Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Egypt; Head of International Publication & Nanotechnology Consultation Center (INCC), Faculty of Pharmacy, Pharos University in Alexandria, Egypt.
| | - Ossama Y Abdallah
- Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Egypt
| |
Collapse
|
|
13
|
Taghe S, Mirzaeei S, Bagheri M. Preparation of polycaprolactone and polymethacrylate nanofibers for controlled ocular delivery of ketorolac tromethamine: Pharmacokinetic study in Rabbit's Eye. Eur J Pharm Sci 2024; 192:106631. [PMID: 37951316 DOI: 10.1016/j.ejps.2023.106631] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2023] [Revised: 10/18/2023] [Accepted: 11/08/2023] [Indexed: 11/13/2023]
Abstract
Ophthalmitis is an inflammation of the eye triggered by various conditions including diseases, allergy, trauma, or surgery. Management of this condition usually includes administration of topical anti-inflammatory eye drops such as nonsteroidal anti-inflammatory drugs. To overcome the challenges of conventional eye drops such as frequent administration and low intraocular bioavailability, nanofibrous inserts of Ketorolac tromethamine (KET) were developed in this study. Polycaprolactone and polymethacrylate containing KET were electrospun to prepare biocompatible and biodegradable nanofibers. The inserts were studied for morphology, drug-polymer interaction, physicochemical properties, cell viability, in vitro drug release study and pharmacokinetic study in rabbit's eye. Uniform nanofibers with mean diameters < 350 nm were developed. Suitable mechanical properties with tensile strength up to 2.8 MPa indicated high strength and flexibility of inserts. Nanofibers exhibited controlled drug release for up to 140 h at a concentration more than 50 μg/ml in tears without causing any damage or irritation to the eye. Formulations indicated enhanced pharmacokinetics with 6- to 8-times higher Area Under the Curve (AUC0-144) compared to KET eye drop. Acceptable cell viability confirmed the safety of inserts. Due to the fact that this preservative-free polymer insert can obtain therapeutic concentration in the tear film without fluctuation, it can be a suitable alternative for the treatment of intraocular inflammations with less complications, easier use, and even higher intraocular penetration.
Collapse
Affiliation(s)
- Shiva Taghe
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran; Pharmaceutical Sciences Research Center, Rahesh Daru Novine, Kermanshah 6715847141, Iran; Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Shahla Mirzaeei
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran; Pharmaceutical Sciences Research Center, Rahesh Daru Novine, Kermanshah 6715847141, Iran; Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.
| | - Masood Bagheri
- Clinical Research Development Center, Imam Khomeini and Mohammad Kermanshahi and Farabi Hospitals, Kermanshah University of Medical Sciences, Kermanshah, Iran; Department of Ophthalmology, Imam Khomeini Eye Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| |
Collapse
|
|
14
|
Kontou EP, Karakosta C, Kounas K, Iatropoulos I, Tsinopoulos I, Kozobolis V, Stavrakas P. Macular Edema Following Silicone Oil Tamponade for Retinal Detachment: A Literature Review. Cureus 2023; 15:e51233. [PMID: 38283484 PMCID: PMC10821764 DOI: 10.7759/cureus.51233] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/28/2023] [Indexed: 01/30/2024] Open
Abstract
Macular edema (ME) is a major cause of reduced vision following intraocular surgery. Although the pathophysiology of ME is not completely understood, inflammatory mediators play a key role. The incidence of ME following pars plana vitrectomy with silicone oil tamponade varies between 13% and 27%. ME usually resolves spontaneously following silicone oil removal, but treatment may be required for resistant cases. In this review, the mechanisms of ME formation after pars plana vitrectomy, its incidence, and its possible therapeutic approaches are discussed.
Collapse
Affiliation(s)
- Evgenia P Kontou
- Department of Ophthalmology, General Hospital of Athens "Korgialeneio-Benakio" Hellenic Red Cross, Athens, GRC
- Department of Ophthalmology, School of Medicine, University of Patras, Patras, GRC
| | - Christina Karakosta
- Department of Ophthalmology, National and Kapodistrian University of Athens School of Medicine, Athens, GRC
| | - Konstantinos Kounas
- Department of Ophthalmology, School of Medicine, University of Patras, Patras, GRC
| | - Ioannis Iatropoulos
- Department of Ophthalmology, School of Medicine, University of Patras, Patras, GRC
| | - Ioannis Tsinopoulos
- Second Department of Ophthalmology, Aristotle University of Thessaloniki, Thessaloniki, GRC
| | - Vassilios Kozobolis
- Department of Ophthalmology, School of Medicine, University of Patras, Patras, GRC
| | - Panagiotis Stavrakas
- Department of Ophthalmology, School of Medicine, University of Patras, Patras, GRC
| |
Collapse
|
|
15
|
Ahmadyar G, Carlson JJ, Kimura A, Alobaidi A, Hallak J, Hansen RN. Real-world treatment patterns and economic burden of post-cataract macular edema. BMC Ophthalmol 2023; 23:380. [PMID: 37723463 PMCID: PMC10506304 DOI: 10.1186/s12886-023-03113-x] [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: 02/14/2023] [Accepted: 08/22/2023] [Indexed: 09/20/2023] Open
Abstract
BACKGROUND Post-cataract macular edema (PCME) is a condition that can occur in patients following cataract surgery without risk factors and complications. Although 80% of patients experience spontaneous resolution after 3 to 12 months, in persistent cases, it can lead to permanent vision loss if left untreated. There are currently no standardized treatment guidelines for PCME, and there have been limited studies showing the impact of PCME on annual Medicare spending and ophthalmology-related outpatient visits per case compared to those without the complication. This study aims to evaluate real-world treatment patterns and the economic burden of patients with PCME. METHODS This retrospective claims analysis identified patients from the IBM® MarketScan® Commercial and Medicare Supplemental databases. Patients with (n = 2430) and without (n = 7290) PCME 1 year post cataract surgery were propensity score matched 1:3 based on age, geographic region, diabetes presence, cataract surgery type, and Charlson Comorbidity Index. Treatment pattern analysis for each PCME patient summarized the distribution of medications across lines of therapy. Economic burden analysis compared the mean number and costs of eye-related outpatient visits, optical coherence tomography imaging scans, and ophthalmic medications between the 2 groups using linear regression models. RESULTS Treatment pattern analysis found 27 different treatment combinations across 6 treatment lines. The most common first-line treatments were topical steroid drops (372 [30%]), topical nonsteroidal anti-inflammatory drug drops (321 [27%]), and intraocular or periocular injectable steroids (189 [15%]). Compared to match controls, PCME patients averaged 6 additional eye-related outpatient office visits (95% CI: 5.7-6.2) resulting in an additional $3,897 (95% CI: $3,475 - $4,319) in total costs. Patients filled 3 more ophthalmology-related outpatient prescription medications (95% CI: 2.8-3.2), adding $371 in total cost (95% CI: $332 - $410). CONCLUSIONS PCME treatment patterns showed wide clinical variability in treatments and time, specifically regarding injectable treatments and combination therapy. Additionally, significantly higher healthcare resource use and economic burden were found for both patients and payers when comparing PCME patients to non-PMCE controls. These results highlight the need for treatment standardization and demonstrate that interventions targeted at preventing PCME may be valuable.
Collapse
Affiliation(s)
- Gina Ahmadyar
- AbbVie Inc, 2525 DuPont Drive, 92612, Irvine, CA, USA.
- School of Pharmacy, University of Washington, 1956 NE Pacific St, HSB H-362, 98195, Seattle, WA, USA.
| | - Josh J Carlson
- School of Pharmacy, University of Washington, 1956 NE Pacific St, HSB H-362, 98195, Seattle, WA, USA
| | - Alan Kimura
- Colorado Retina Associates, 255 S. Routt St., Suite 200, 80228, Lakewood, CO, USA
| | - Ali Alobaidi
- AbbVie Inc, 2525 DuPont Drive, 92612, Irvine, CA, USA
| | - Joelle Hallak
- AbbVie Inc, 2525 DuPont Drive, 92612, Irvine, CA, USA
| | - Ryan N Hansen
- School of Pharmacy, University of Washington, 1956 NE Pacific St, HSB H-362, 98195, Seattle, WA, USA
| |
Collapse
|
|
16
|
Fathalla Z, Fatease AA, Abdelkader H. Formulation and In-Vitro/Ex-Vivo Characterization of Pregelled Hybrid Alginate-Chitosan Microparticles for Ocular Delivery of Ketorolac Tromethamine. Polymers (Basel) 2023; 15:2773. [PMID: 37447419 DOI: 10.3390/polym15132773] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2023] [Revised: 06/13/2023] [Accepted: 06/19/2023] [Indexed: 07/15/2023] Open
Abstract
Innovative hybrid chitosan-sodium alginate (Ch-Ag) microparticles (MPs) were fabricated using both the ionic gelation method as well as the pre-gelation technique. The hybrid Ch-Ag MPs were studied for size, zeta potential, morphology, mucoadhesion, in-vitro release, corneal permeation, and ocular irritation using lens and corneal epithelial cell lines. The average particle size ranged from 1322 nm to 396 nm. The zeta potential for the prepared formulations showed an increase with increasing Ch concentrations up to a value of >35 mV; the polydispersity index (PDI) of some optimized MPs was around 0.1. Compared to drug-free MPs, ketorolac-loaded Ch-Ag MPs demonstrated a drug proportion-dependent increase in their size. SEM, as well as TEM of KT-loaded MPs, confirmed that the formed particles were quasi-spherical to elliptical in shape. The KT release from the MPs demonstrated a prolonged release profile in comparison to the control KT solution. Further, mucoadhesion studies with porcine mucin revealed that the KT-loaded MPs had effective mucoadhesive properties, and polymeric particles were stable in the presence of mucin. Corneal permeation was studied on bovine eyes, and the results revealed that Ch-based MPs were capable of showing more sustained KT release across the cornea compared with that for the control drug solution. Conclusively, the cytotoxicity assay confirmed that the investigated MPs were non-irritant and could confer protection from direct drug irritation of KT on the ocular surface. The MTT cytotoxicity assay confirmed that KT-loaded MPs showed acceptable and reasonable tolerability with both human lens and corneal epithelial cell lines compared to the control samples.
Collapse
Affiliation(s)
- Zeinab Fathalla
- Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia 61519, Egypt
| | - Adel Al Fatease
- Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha 62223, Saudi Arabia
| | - Hamdy Abdelkader
- Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha 62223, Saudi Arabia
| |
Collapse
|
|
17
|
Gabr AF, Kamel MF, Elbarawy AA. Topical bromfenac as adjunctive treatment with intravitreal ranibizumab for diabetic macular edema. Int Ophthalmol 2023:10.1007/s10792-023-02722-1. [PMID: 37083870 PMCID: PMC10400663 DOI: 10.1007/s10792-023-02722-1] [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: 02/04/2023] [Accepted: 04/09/2023] [Indexed: 04/22/2023]
Abstract
PURPOSE To determine the safety and efficacy of adding topical bromfenac 0.09% in the treatment of diabetic macular edema. METHODS Seventy patients (70 eyes) with center involved diabetic macular edema with macular thickness (300-500 μm) were included. Patients were divided randomly into two groups: 35 eyes in each group. Both groups were treated with intravitreal ranibizumab monthly for three consecutive months. Bromfenac 0.09% eye drops twice daily was added to the treatment of study group for six months from commencement of treatment. The efficacy of topical bromfenac was evaluated by comparing both groups through follow-up period as regards to visual acuity, central and average thickness and the need for re-injection. RESULTS Patients treated with topical bromfenac in addition to intravitreal ranibizumab revealed significant improvement in visual acuity, more reduction in central and average macular thickness and less tendency to need reinjection compared to those treated with ranibizumab alone (p 0.013, p 0.010 and p 0.022, respectively). No side effects was encountered with the use of topical bromfenac. CONCLUSION Topical bromfenac 0.09% twice a day could enhance and sustain the efficacy of intravitreal ranibizumab in the treatment of diabetic macular edema without increasing the incidence of corneal side effects.
Collapse
Affiliation(s)
- Ahmed F Gabr
- Ophthalmology Department, Faculty of Medicine, Aswan University, Aswan, Egypt.
| | - Marian F Kamel
- Ophthalmology Department, Faculty of Medicine, Aswan University, Aswan, Egypt
| | - Ahmed A Elbarawy
- Ophthalmology Department, Faculty of Medicine, Aswan University, Aswan, Egypt
| |
Collapse
|
|
18
|
Thermoresponsive in-situ gel containing hyaluronic acid and indomethacin for the treatment of corneal chemical burn. Int J Pharm 2023; 631:122468. [PMID: 36503038 DOI: 10.1016/j.ijpharm.2022.122468] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Revised: 11/20/2022] [Accepted: 12/04/2022] [Indexed: 12/13/2022]
Abstract
Ocular chemical burns are prevalent injuries that must have immediate and effective treatment to avoid complications. Aiming to improve bioavailability and efficacy, a poloxamer-based thermoresponsive in-situ gelling system containing hyaluronic acid and indomethacin was developed. Formulations with different polymeric proportions were screened through rheological measurements resulting in an optimized system (F2) with gelling temperature of 34.2 ± 0.11 °C. Its maximum viscosity varied from 77.33 mPa (25 °C) to 82.95 mPa (34 °C) following a non-Newtonian profile and a pH of 6.86 ± 0.01. No incompatibilities were found after infrared analysis. Polarized light microscopy and cryo-transmission electron microscopy have demonstrated micelles of nano-sized dimensions (21.86 nm) with indomethacin entrapped in the core, forming a polymeric network under heating. In vitro tests revealed a cumulative release of 59.75 ± 3.17 % up to 24 h under a sustained release profile. Results from HET-CAM assay indicated that F2 was well tolerated. Corneal wound healing was significantly faster in animals treated with F2 compared to a commercial formulation and an untreated group. These findings suggests that F2 could be an efficient system to delivery drugs into the ocular surface improving wound healing.
Collapse
|
|
19
|
Secretome of human umbilical cord mesenchymal stem cell maintains skin homeostasis by regulating multiple skin physiological function. Cell Tissue Res 2023; 391:111-125. [PMID: 36241740 DOI: 10.1007/s00441-022-03697-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 10/05/2022] [Indexed: 01/18/2023]
Abstract
Skin is the largest organ in the body and the first defense to resist various diseases and external stimuli that easily cause infection and inflammation. Aseptic inflammation, barrier damage, and foreign aid pressure induce the destruction and damage to the skin microenvironment. Subsequently, it destroys the skin's physiological function, leading to the maintenance and circulation of steady-state imbalance and aggravating the process of skin disorders. Our study evaluated the therapeutic potential of the secretome of human umbilical cord mesenchymal stem cells (UC-CM) for dermatological diseases in adult human skin cells, ex vivo skin tissue, and a 3D skin model. Our data suggested several advantages of UC-CM due to (1) their low cytotoxicity and sensitization properties; (2) their anti-inflammatory capacity for treating inflammatory chronic cutaneous diseases; (3) their enhanced capacity of the skin barrier for treating abnormal barrier metabolism; and (4) their positive impact on restoring skin homeostasis due to effective regulation ability of skin physiological function including cell apoptosis, detoxification, and anti-aging. We thus envisage that the possibility of harnessing the therapeutic potential of UC-CM might benefit patients suffering from inflammatory skin disorders such as atopic dermatitis, acne, and psoriasis.
Collapse
|
|
20
|
Balasubramaniam B, Chong YJ, Azzopardi M, Logeswaran A, Denniston AK. Topical Anti-Inflammatory Agents for Non-Infectious Uveitis: Current Treatment and Perspectives. J Inflamm Res 2022; 15:6439-6451. [PMID: 36467992 PMCID: PMC9717596 DOI: 10.2147/jir.s288294] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Accepted: 11/12/2022] [Indexed: 10/07/2023] Open
Abstract
Non-infectious uveitis represents a heterogenous group of immune-mediated ocular diseases, which can be associated with underlying systemic disease. While the initial choice of treatment of non-infectious uveitis depends on a number of factors such as anatomical location and degree of inflammation, topical therapies often remain the initial choice of non-invasive therapy. In this narrative review, we aim to describe the literature on non-infectious uveitis, with specific focus on the current perspective on topical anti-inflammatory therapy.
Collapse
Affiliation(s)
- Balini Balasubramaniam
- Ophthalmology Department, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, B15 2TH, UK
| | - Yu Jeat Chong
- Birmingham & Midland Eye Centre, Birmingham, B18 7QH, UK
| | - Matthew Azzopardi
- Ophthalmology Department, Royal London Hospital, Barts Health NHS Trust, London, E1 1BB, UK
| | | | - Alastair K Denniston
- Ophthalmology Department, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, B15 2TH, UK
| |
Collapse
|
|
21
|
Romeo A, Bonaccorso A, Carbone C, Lupo G, Daniela Anfuso C, Giurdanella G, Caggia C, Randazzo C, Russo N, Romano GL, Bucolo C, Rizzo M, Tosi G, Thomas Duskey J, Ruozi B, Pignatello R, Musumeci T. Melatonin loaded hybrid nanomedicine: DoE approach, optimization and in vitro study on diabetic retinopathy model. Int J Pharm 2022; 627:122195. [PMID: 36115466 DOI: 10.1016/j.ijpharm.2022.122195] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 09/03/2022] [Accepted: 09/09/2022] [Indexed: 11/17/2022]
Abstract
Melatonin (MEL) is a pleiotropic neurohormone of increasing interest as a neuroprotective agent in ocular diseases. Improving the mucoadhesiveness is a proposed strategy to increase the bioavailability of topical formulations. Herein, the design and optimization of MEL-loaded lipid-polymer hybrid nanoparticles (mel-LPHNs) using Design of Experiment (DoE) was performed. LPHNs consisted of PLGA-PEG polymer nanoparticles coated with a cationic lipid-shell. The optimized nanomedicine showed suitable size for ophthalmic administration (189.4 nm; PDI 0.260) with a positive surface charge (+39.8 mV), high encapsulation efficiency (79.8 %), suitable pH and osmolarity values, good mucoadhesive properties and a controlled release profile. Differential Scanning Calorimetry and Fourier-Transform Infrared Spectroscopy confirmed the encapsulation of melatonin in the systems and the interaction between lipids and polymer matrix. Biological evaluation in an in vitro model of diabetic retinopathy demonstrated enhanced neuroprotective and antioxidant activities of mel-LPHNs, compared to melatonin aqueous solution at the same concentration (0.1 and 1 μM). A modified Draize test was performed to assess the ocular tolerability of the formulation showing no signs of irritation. To the best our knowledge, this study reported for the first time the development of mel-LPHNs, a novel and safe hybrid platform suitable for the topical management of retinal diseases.
Collapse
Affiliation(s)
- Alessia Romeo
- Department of Drug and Health Sciences, University of Catania, Viale A. Doria, 6 - 95125 Catania, Italy.
| | - Angela Bonaccorso
- Department of Drug and Health Sciences, University of Catania, Viale A. Doria, 6 - 95125 Catania, Italy; Department of Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 97, 95123 Catania, Italy.
| | - Claudia Carbone
- Department of Drug and Health Sciences, University of Catania, Viale A. Doria, 6 - 95125 Catania, Italy; Department of Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 97, 95123 Catania, Italy.
| | - Gabriella Lupo
- Department of Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 97, 95123 Catania, Italy.
| | - Carmelina Daniela Anfuso
- Department of Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 97, 95123 Catania, Italy.
| | - Giovanni Giurdanella
- Department of Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 97, 95123 Catania, Italy.
| | - Cinzia Caggia
- NANO-i, Research Centre for Ocular Nanotechnology, University of Catania, Viale A. Doria 6, 95125 Catania, Italy; Department of Agriculture, Food and Environment (Di3A), University of Catania, Via S. Sofia 100, 95123 Catania, Italy.
| | - Cinzia Randazzo
- NANO-i, Research Centre for Ocular Nanotechnology, University of Catania, Viale A. Doria 6, 95125 Catania, Italy; Department of Agriculture, Food and Environment (Di3A), University of Catania, Via S. Sofia 100, 95123 Catania, Italy.
| | - Nunziatina Russo
- Department of Agriculture, Food and Environment (Di3A), University of Catania, Via S. Sofia 100, 95123 Catania, Italy.
| | - Giovanni Luca Romano
- Department of Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 97, 95123 Catania, Italy.
| | - Claudio Bucolo
- Department of Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 97, 95123 Catania, Italy.
| | - Milena Rizzo
- Department of Drug and Health Sciences, University of Catania, Viale A. Doria, 6 - 95125 Catania, Italy.
| | - Giovanni Tosi
- Department of Life Sciences, Nanotech Lab, Te.Far.T.I., University of Modena & Reggio Emilia, Via Campi 103, Modena 41125, Italy.
| | - Jason Thomas Duskey
- Department of Life Sciences, Nanotech Lab, Te.Far.T.I., University of Modena & Reggio Emilia, Via Campi 103, Modena 41125, Italy.
| | - Barbara Ruozi
- Department of Life Sciences, Nanotech Lab, Te.Far.T.I., University of Modena & Reggio Emilia, Via Campi 103, Modena 41125, Italy.
| | - Rosario Pignatello
- Department of Drug and Health Sciences, University of Catania, Viale A. Doria, 6 - 95125 Catania, Italy; NANO-i, Research Centre for Ocular Nanotechnology, University of Catania, Viale A. Doria 6, 95125 Catania, Italy.
| | - Teresa Musumeci
- Department of Drug and Health Sciences, University of Catania, Viale A. Doria, 6 - 95125 Catania, Italy; NANO-i, Research Centre for Ocular Nanotechnology, University of Catania, Viale A. Doria 6, 95125 Catania, Italy.
| |
Collapse
|
|
22
|
Ricci F, Racaniello GF, Lopedota A, Laquintana V, Arduino I, Lopalco A, Cutrignelli A, Franco M, Sigurdsson HH, Denora N. Chitosan/sulfobutylether-β-cyclodextrin based nanoparticles coated with thiolated hyaluronic acid for indomethacin ophthalmic delivery. Int J Pharm 2022; 622:121905. [PMID: 35697201 DOI: 10.1016/j.ijpharm.2022.121905] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Revised: 06/03/2022] [Accepted: 06/07/2022] [Indexed: 12/18/2022]
Abstract
Indomethacin (IND) is topically administered for the treatment of the anterior segment diseases such as conjunctivitis, uveitis, and inflammation prevention for post-cataract surgery, as well as posterior segment diseases as macular edema. Currently IND is available as 0.1% w/v hydroxypropyl-β-cyclodextrin-based eye drop formulation and its bioavailability is limited by several drawbacks such as the nasolacrimal duct draining, the reflex blinking and the low volume of the conjunctival sac. In this study, chitosan (CS)/sulfobutylether-β-cyclodextrin (SBE-β-CD) based nanoparticles (NPs) with a mean diameter of 340 (±7) nm, a ζ-potential value of +18.3 (±0.5) mV and coated with thiolated low molecular weight hyaluronic acid were formulated to improve both the solubility and the residential time in the conjunctival sac of the loaded drug IND. The NPs were prepared through the ionotropic gelation technique, exploiting the interaction between the positively charged amino group of CS and the negatively charged sulfonic group of SBE-β-CD. The mucoadhesive properties of the NPs were evaluated on chicken trachea and esophagus tissues using a texture analyser. The irritability effects of NPs were disclaimed with Hecam test. The developed coated NPs showed increased residential time in the conjunctival sac, displayed no irritancy or toxicity for local administration, making them an optimal and innovative drug delivery system for the treatment of anterior segment inflammation diseases. On the other hand, the uncoated NPs displayed better permeating properties since they are smaller and could be further exploited for the treatment of posterior segment diseases.
Collapse
Affiliation(s)
- Fabrizio Ricci
- Department of Pharmacy - Pharmaceutical Sciences, University of Bari "Aldo Moro", 70125 Bari, Italy; Department of Pharmaceutical Technology, University of Innsbruck, Institute of Pharmacy, Center for Chemistry and Biomedicine, 6020 Innsbruck, Austria
| | | | - Angela Lopedota
- Department of Pharmacy - Pharmaceutical Sciences, University of Bari "Aldo Moro", 70125 Bari, Italy
| | - Valentino Laquintana
- Department of Pharmacy - Pharmaceutical Sciences, University of Bari "Aldo Moro", 70125 Bari, Italy
| | - Ilaria Arduino
- Department of Pharmacy - Pharmaceutical Sciences, University of Bari "Aldo Moro", 70125 Bari, Italy
| | - Antonio Lopalco
- Department of Pharmacy - Pharmaceutical Sciences, University of Bari "Aldo Moro", 70125 Bari, Italy
| | - Annalisa Cutrignelli
- Department of Pharmacy - Pharmaceutical Sciences, University of Bari "Aldo Moro", 70125 Bari, Italy
| | - Massimo Franco
- Department of Pharmacy - Pharmaceutical Sciences, University of Bari "Aldo Moro", 70125 Bari, Italy
| | | | - Nunzio Denora
- Department of Pharmacy - Pharmaceutical Sciences, University of Bari "Aldo Moro", 70125 Bari, Italy.
| |
Collapse
|
|
23
|
Ishkhanyan H, Ziolek RM, Barlow DJ, Lawrence MJ, Poghosyan AH, Lorenz CD. NSAID solubilisation promotes morphological transitions in Triton X-114 surfactant micelles. J Mol Liq 2022. [DOI: 10.1016/j.molliq.2022.119050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
|
|
24
|
Lin X, Liu J, Zhou F, Ou Y, Rong J, Zhao J. Poly(2-hydroxyethyl methacrylate-co-quaternary ammonium salt chitosan) hydrogel: A potential contact lens material with tear protein deposition resistance and antimicrobial activity. BIOMATERIALS ADVANCES 2022; 136:212787. [PMID: 35929300 DOI: 10.1016/j.bioadv.2022.212787] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Revised: 03/17/2022] [Accepted: 04/01/2022] [Indexed: 06/15/2023]
Abstract
Tear protein deposition resistance and antimicrobial property are two challenges of conventional poly(2-hydroxyethyl methacrylate) (pHEMA) contact lenses. In this work, we developed a poly(2-hydroxyethyl methacrylate-co-quaternary ammonium salt chitosan) hydrogel, named as p(HEMA-co-mHACC) hydrogel, using acryloyl HACC (mHACC) as a macromolecular crosslinker. With increasing the acryloyl substitution degree (14-29%) or mHACC content (2-11%), the hydrogel showed an enhanced tensile strength (432-986 kPa) and Young's modulus (360-1158 kPa), a decreased elongation at break (242-84%), and an increased visible light transmittance (0-95%). At an optimal acryloyl substitution degree of 26%, with the increase of mHACC content from 2% to 11%, p(HEMA-co-mHACC) hydrogel presented a decreased water contact angle from 84.6 to 55.3 degree, an increased equilibrium water content from 38% to 45%, and an enhanced oxygen permeability from 8.5 to 13.5 barrer. Due to the enhancement in surface hydrophilicity and electropositivity, p(HEMA-co-mHACC) hydrogel remarkably reduced the deposition of lysozyme, but little affected the adsorption of BSA, depending on the hydrophilic/hydrophobic and electrostatic interactions. The antimicrobial test against Staphylococcus aureus and Escherichia coli showed that p(HEMA-co-mHACC) hydrogel presented an 8-32 times higher germicidal ability than pHEMA hydrogel, indicative of a better antimicrobial activity. The in vitro cell culture of mouse NIH3T3 fibroblasts and immortalized human keratinocytes showed that p(HEMA-co-mHACC) hydrogel was non-toxic. Thus, p(HEMA-co-mHACC) hydrogel with tear protein deposition resistance and antimicrobial activity is a potential candidate for contact lenses.
Collapse
Affiliation(s)
- Xilin Lin
- Department of Materials Science and Engineering, College of Chemistry and Materials Science, Jinan University, Guangzhou 511436, China
| | - Jinqiang Liu
- Department of Materials Science and Engineering, College of Chemistry and Materials Science, Jinan University, Guangzhou 511436, China
| | - Fei Zhou
- Department of Materials Science and Engineering, College of Chemistry and Materials Science, Jinan University, Guangzhou 511436, China
| | - Yangtao Ou
- Department of Materials Science and Engineering, College of Chemistry and Materials Science, Jinan University, Guangzhou 511436, China
| | - Jianhua Rong
- Department of Materials Science and Engineering, College of Chemistry and Materials Science, Jinan University, Guangzhou 511436, China; Engineering Research Center of Artificial Organs and Materials, Ministry of Education, Guangzhou 511436, China
| | - Jianhao Zhao
- Department of Materials Science and Engineering, College of Chemistry and Materials Science, Jinan University, Guangzhou 511436, China; Engineering Research Center of Artificial Organs and Materials, Ministry of Education, Guangzhou 511436, China.
| |
Collapse
|
|
25
|
Hosseinian H, Hosseini S, Martinez-Chapa SO, Sher M. A Meta-Analysis of Wearable Contact Lenses for Medical Applications: Role of Electrospun Fiber for Drug Delivery. Polymers (Basel) 2022; 14:185. [PMID: 35012207 PMCID: PMC8747307 DOI: 10.3390/polym14010185] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2021] [Revised: 12/18/2021] [Accepted: 12/20/2021] [Indexed: 01/14/2023] Open
Abstract
In recent years, wearable contact lenses for medical applications have attracted significant attention, as they enable continuous real-time recording of physiological information via active and noninvasive measurements. These devices play a vital role in continuous monitoring of intraocular pressure (IOP), noninvasive glucose monitoring in diabetes patients, drug delivery for the treatment of ocular illnesses, and colorblindness treatment. In specific, this class of medical devices is rapidly advancing in the area of drug loading and ocular drug release through incorporation of electrospun fibers. The electrospun fiber matrices offer a high surface area, controlled morphology, wettability, biocompatibility, and tunable porosity, which are highly desirable for controlled drug release. This article provides an overview of the advances of contact lens devices in medical applications with a focus on four main applications of these soft wearable devices: (i) IOP measurement and monitoring, (ii) glucose detection, (iii) ocular drug delivery, and (iv) colorblindness treatment. For each category and application, significant challenges and shortcomings of the current devices are thoroughly discussed, and new areas of opportunity are suggested. We also emphasize the role of electrospun fibers, their fabrication methods along with their characteristics, and the integration of diverse fiber types within the structure of the wearable contact lenses for efficient drug loading, in addition to controlled and sustained drug release. This review article also presents relevant statistics on the evolution of medical contact lenses over the last two decades, their strengths, and the future avenues for making the essential transition from clinical trials to real-world applications.
Collapse
Affiliation(s)
- Hamed Hosseinian
- School of Engineering and Sciences, Tecnologico de Monterrey, Ave. Eugenio Garza Sada 2501, Monterrey 64849, Mexico; (H.H.); (S.O.M.-C.)
| | - Samira Hosseini
- School of Engineering and Sciences, Tecnologico de Monterrey, Ave. Eugenio Garza Sada 2501, Monterrey 64849, Mexico; (H.H.); (S.O.M.-C.)
- Writing Lab, Institute for the Future of Education, Tecnologico de Monterrey, Monterrey 64849, Mexico
| | - Sergio O. Martinez-Chapa
- School of Engineering and Sciences, Tecnologico de Monterrey, Ave. Eugenio Garza Sada 2501, Monterrey 64849, Mexico; (H.H.); (S.O.M.-C.)
| | - Mazhar Sher
- Department of Mechanical Engineering and Applied Mechanics, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA 19104, USA
| |
Collapse
|
|
26
|
Kasza K, Gurnani P, Hardie KR, Cámara M, Alexander C. Challenges and solutions in polymer drug delivery for bacterial biofilm treatment: A tissue-by-tissue account. Adv Drug Deliv Rev 2021; 178:113973. [PMID: 34530014 DOI: 10.1016/j.addr.2021.113973] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Revised: 08/12/2021] [Accepted: 09/08/2021] [Indexed: 02/07/2023]
Abstract
To tackle the emerging antibiotic resistance crisis, novel antimicrobial approaches are urgently needed. Bacterial communities (biofilms) are a particular concern in this context. Biofilms are responsible for most human infections and are inherently less susceptible to antibiotic treatments. Biofilms have been linked with several challenging chronic diseases, including implant-associated osteomyelitis and chronic wounds. The specific local environments present in the infected tissues further contribute to the rise in antibiotic resistance by limiting the efficacy of systemic antibiotic therapies and reducing drug concentrations at the infection site, which can lead to reoccurring infections. To overcome the shortcomings of systemic drug delivery, encapsulation within polymeric carriers has been shown to enhance antimicrobial efficacy, permeation and retention at the infection site. In this Review, we present an overview of current strategies for antimicrobial encapsulation within polymeric carriers, comparing challenges and solutions on a tissue-by-tissue basis. We compare challenges and proposed drug delivery solutions from the perspective of the local environments for biofilms found in oral, wound, gastric, urinary tract, bone, pulmonary, vaginal, ocular and middle/inner ear tissues. We will also discuss future challenges and barriers to clinical translation for these therapeutics. The following Review demonstrates there is a significant imbalance between the research focus being placed on different tissue types, with some targets (oral and wound biofims) being extensively more studied than others (vaginal and otitis media biofilms and endocarditis). Furthermore, the importance of the local tissue environment when selecting target therapies is demonstrated, with some materials being optimal choices for certain sites of bacterial infection, while having limited applicability in others.
Collapse
|
|
27
|
El Moussaoui S, Abo-Horan I, Halbaut L, Alonso C, Coderch L, Garduño-Ramírez ML, Clares B, Soriano JL, Calpena AC, Fernández-Campos F, Mallandrich M. Polymeric Nanoparticles and Chitosan Gel Loading Ketorolac Tromethamine to Alleviate Pain Associated with Condyloma Acuminata during the Pre- and Post-Ablation. Pharmaceutics 2021; 13:pharmaceutics13111784. [PMID: 34834198 PMCID: PMC8618351 DOI: 10.3390/pharmaceutics13111784] [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] [Received: 08/31/2021] [Revised: 09/25/2021] [Accepted: 10/20/2021] [Indexed: 11/21/2022] Open
Abstract
This study describes the preparation and evaluation of two formulations, a hydrogel and a nanostructured system, containing ketorolac tromethamine as an anti-inflammatory agent for the local therapy against the inflammatory process derived from the surgical excision of Condyloma acuminata. Both formulations were physicochemically characterized. In vitro release profiles show that the nanoparticles release 92% ± 2.3 of the total ketorolac tromethamine encapsulated, while the chitosan gel releases 18.6% ± 0.2. The ex vivo permeation and distribution through human skin were also assayed and was observed how the main amount of ketorolac tromethamine is retained in the epidermis. In vivo studies were accomplished to evaluate the anti-inflammatory efficacy in mice which also involved the histological analysis to confirm the in vivo results. The nanoparticles present a significantly higher anti-inflammatory efficacy than chitosan gel. The tolerability of developed formulations was assessed by monitoring the biomechanical properties of the skin before and after application of both formulations. No statistical differences in trans-epidermal water loss and skin hydration with respect to the basal values were observed and the formulations exhibited higher anti-inflammatory activity compared to a reference ketotorlac tromethamine solution. Therefore, it can be concluded that both formulations can be proposed as outstanding candidates for offering a local anti-inflammatory therapeutical tool with potential clinical application.
Collapse
Affiliation(s)
- Salima El Moussaoui
- Department of Pharmacy, Pharmaceutical Technology and Physical-Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Av. Joan XXIII 27-31, 08028 Barcelona, Spain; (S.E.M.); (I.A.-H.); (L.H.); (A.C.C.); (M.M.)
| | - Ismael Abo-Horan
- Department of Pharmacy, Pharmaceutical Technology and Physical-Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Av. Joan XXIII 27-31, 08028 Barcelona, Spain; (S.E.M.); (I.A.-H.); (L.H.); (A.C.C.); (M.M.)
| | - Lyda Halbaut
- Department of Pharmacy, Pharmaceutical Technology and Physical-Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Av. Joan XXIII 27-31, 08028 Barcelona, Spain; (S.E.M.); (I.A.-H.); (L.H.); (A.C.C.); (M.M.)
| | - Cristina Alonso
- Institute of Advanced Chemistry of Catalonia-CSIC (IQAC-CSIC), 18-26 Jordi Girona St., 08034 Barcelona, Spain; (C.A.); (L.C.)
| | - Lluïsa Coderch
- Institute of Advanced Chemistry of Catalonia-CSIC (IQAC-CSIC), 18-26 Jordi Girona St., 08034 Barcelona, Spain; (C.A.); (L.C.)
| | - María Luisa Garduño-Ramírez
- Centro de Investigaciones Químicas, Universidad Autónoma del Estado de Morelos, Avenida Universidad 1001, Cuernavaca 62209, Mexico;
| | - Beatriz Clares
- Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Granada, 18071 Granada, Spain;
- Institut de Nanociència i Nanotecnologia IN2UB, Universitat de Barcelona, 08028 Barcelona, Spain
- Correspondence:
| | - José Luis Soriano
- Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Granada, 18071 Granada, Spain;
| | - Ana Cristina Calpena
- Department of Pharmacy, Pharmaceutical Technology and Physical-Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Av. Joan XXIII 27-31, 08028 Barcelona, Spain; (S.E.M.); (I.A.-H.); (L.H.); (A.C.C.); (M.M.)
- Institut de Nanociència i Nanotecnologia IN2UB, Universitat de Barcelona, 08028 Barcelona, Spain
| | | | - Mireia Mallandrich
- Department of Pharmacy, Pharmaceutical Technology and Physical-Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Av. Joan XXIII 27-31, 08028 Barcelona, Spain; (S.E.M.); (I.A.-H.); (L.H.); (A.C.C.); (M.M.)
- Institut de Nanociència i Nanotecnologia IN2UB, Universitat de Barcelona, 08028 Barcelona, Spain
| |
Collapse
|
|
28
|
Chen C, Wang C, Zhou X, Xu L, Chen H, Qian K, Jia B, Su G, Fu J. Nonsteroidal anti-inflammatory drugs for retinal neurodegenerative diseases. Prostaglandins Other Lipid Mediat 2021; 156:106578. [PMID: 34245897 DOI: 10.1016/j.prostaglandins.2021.106578] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Revised: 06/29/2021] [Accepted: 07/06/2021] [Indexed: 10/20/2022]
Abstract
Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most common prescription drugs for inflammation, and topical NSAIDs are often used in ophthalmology to reduce pain, photophobia, inflammation, and edema. In recent years, many published reports have found that NSAIDs play an important role in the treatment of retinal neurodegenerative diseases, such as age-related macular degeneration (AMD), diabetic retinopathy (DR), glaucoma, pathological myopia, and retinitis pigmentosa (RP). The aim of the current review is to provide an overview of the role of various NSAIDs in the treatment of retinal neurodegenerative diseases and the corresponding mechanisms of action. This review highlighted that the topical application of NSAIDs for the treatment of retinal degenerative diseases has been studied to a remarkable extent and that its beneficial effects in many diseases have been proven. In the future, prospective studies with large study populations are required to extend these effects to clinical settings.
Collapse
Affiliation(s)
- Chen Chen
- Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, Jilin, China.
| | - Chenguang Wang
- Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, Jilin, China.
| | - Xuebin Zhou
- Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, Jilin, China.
| | - Lingxian Xu
- Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, Jilin, China.
| | - Han Chen
- Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, Jilin, China.
| | - Kun Qian
- Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, Jilin, China.
| | - Bo Jia
- Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, Jilin, China.
| | - Guanfang Su
- Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, Jilin, China.
| | - Jinling Fu
- Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, Jilin, China.
| |
Collapse
|
|
29
|
Efficacy and Safety of Topical Dosage Forms of Non-Steroidal Anti-Inflammatory Drugs and their Pharmacokinetic Determinants (Review). Pharm Chem J 2021. [DOI: 10.1007/s11094-021-02446-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
|
|
30
|
Hoang C, Nguyen AK, Nguyen TQ, Fang W, Han B, Hoang BX, Tran HD. Application of Dimethyl Sulfoxide as a Therapeutic Agent and Drug Vehicle for Eye Diseases. J Ocul Pharmacol Ther 2021; 37:441-451. [PMID: 34314611 DOI: 10.1089/jop.2021.0043] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023] Open
Abstract
Dimethyl sulfoxide (DMSO) is an amphipathic molecule widely used as a solvent for water-insoluble substances, cryopreserving, and cell-biological therapies. It has known properties as an inducer of cellular differentiation, a free radical scavenger, and a radioprotectant. In addition, DMSO is used for its various therapeutic and pharmaceutical properties, such as anti-inflammatory, local and systemic analgesic, antibacterial, antifungal, antiviral, and membrane penetration enhancement agents. DMSO treatment can be given orally, intravenously, or topically for a wide range of indications. The administration of DMSO exhibits favorable outcomes in human eye diseases with low to none observed ocular or systemic ocular toxicity. Nevertheless, DMSO is an essential and nonpatentable potential therapeutic agent that remains underexplored and ignored by pharmaceutical developers and ophthalmologists. This current review takes data from experimental and clinical studies that have been published to substantiate the potential therapeutic efficacy of DMSO and stimulate the research of its application in clinical ophthalmology. Given that DMSO is inexpensive, safe, and easily formulated into therapeutic medicinal products and conventional ophthalmological drugs, this compound should be further explored and studied in the treatment of a variety of acute and chronic ocular disorders.
Collapse
Affiliation(s)
- Cuong Hoang
- Department of Training and Social Relationship, National Ophthalmological Hospital, Hanoi, Vietnam
| | - Anh Kim Nguyen
- Inventive Medical Foundation, South El Monte, California, USA
| | | | - William Fang
- Western University of Health Sciences, Pomona, California, USA
| | - Bo Han
- Department of Surgery, Keck School of Medicine University of Southern California, Los Angeles, California, USA
| | - Ba X Hoang
- Department of Surgery, Keck School of Medicine University of Southern California, Los Angeles, California, USA
| | - Hau D Tran
- Department of Oncology, National Children Hospital, Hanoi, Vietnam
| |
Collapse
|
|
31
|
Smail SS, Ghareeb MM, Omer HK, Al-Kinani AA, Alany RG. Studies on Surfactants, Cosurfactants, and Oils for Prospective Use in Formulation of Ketorolac Tromethamine Ophthalmic Nanoemulsions. Pharmaceutics 2021; 13:pharmaceutics13040467. [PMID: 33808316 PMCID: PMC8065503 DOI: 10.3390/pharmaceutics13040467] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 03/24/2021] [Accepted: 03/27/2021] [Indexed: 11/16/2022] Open
Abstract
Nanoemulsions (NE) are isotropic, dispersions of oil, water, surfactant(s) and cosurfactant(s). A range of components (11 surfactants, nine cosurfactants, and five oils) were investigated as potential excipients for preparation of ketorolac tromethamine (KT) ocular nanoemulsion. Diol cosurfactants were investigated for the effect of their carbon chain length and dielectric constant (DEC), Log P, and HLB on saturation solubility of KT. Hen's Egg Test-ChorioAllantoic Membrane (HET-CAM) assay was used to evaluate conjunctival irritation of selected excipients. Of the investigated surfactants, Tween 60 achieved the highest KT solubility (9.89 ± 0.17 mg/mL), followed by Cremophor RH 40 (9.00 ± 0.21 mg/mL); amongst cosurfactants of interest ethylene glycol yielded the highest KT solubility (36.84 ± 0.40 mg/mL), followed by propylene glycol (26.23 ± 0.82 mg/mL). The solubility of KT in cosurfactants was affected by four molecular descriptors: carbon chain length, DEC, log P and HLB. KT solubility was directly proportional to DEC and the HLB yet, inversely proportional to carbon chain length and log P. All surfactants, except Labrasol ALF, were non-irritant. The majority of cosurfactants were slightly irritant, butylene glycol was a moderate irritant, pentylene and hexylene glycols were strong irritants. These findings will inform experiments aimed at developing NE formulations for ocular administration of KT.
Collapse
Affiliation(s)
- Shahla S. Smail
- Drug Discovery, Delivery and Patient Care (DDDPC) Theme, Department of Pharmacy, Kingston University, Kingston upon Thames, London KT1 2EE, UK;
- Department of Pharmaceutics, College of Pharmacy, Hawler Medical University, Kurdistan Region, Erbil 44001, Iraq;
- Correspondence: (S.S.S.); (A.A.A.-K.)
| | - Mowafaq M. Ghareeb
- Department of Pharmaceutics, College of Pharmacy, University of Baghdad, Baghdad 10011, Iraq;
| | - Huner K. Omer
- Department of Pharmaceutics, College of Pharmacy, Hawler Medical University, Kurdistan Region, Erbil 44001, Iraq;
| | - Ali A. Al-Kinani
- Drug Discovery, Delivery and Patient Care (DDDPC) Theme, Department of Pharmacy, Kingston University, Kingston upon Thames, London KT1 2EE, UK;
- Correspondence: (S.S.S.); (A.A.A.-K.)
| | - Raid G. Alany
- Drug Discovery, Delivery and Patient Care (DDDPC) Theme, Department of Pharmacy, Kingston University, Kingston upon Thames, London KT1 2EE, UK;
- School of Pharmacy, The University of Auckland, Auckland 1023, New Zealand
| |
Collapse
|
|
32
|
Wróblewska KB, Plewa S, Długaszewska J, Froelich A, Muszalska-Kolos I. Design and evaluation of pharmaceutical availability, stability and quality of modified viscosity eye drops with choline salicylate. Eur J Pharm Sci 2021; 159:105725. [PMID: 33482319 DOI: 10.1016/j.ejps.2021.105725] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Revised: 01/08/2021] [Accepted: 01/13/2021] [Indexed: 11/25/2022]
Abstract
These studies investigate the possibility of developing and using choline salicylate (CS) in ophthalmic therapy in the form of eye drops with increased viscosity. A 0.5% addition of hydroxypropyl methylcellulose (HPMC) was used as the viscosity increasing agent. The ability of CS to cross a hydrophilic membrane (regenerated cellulose membrane) was assessed by determining a rate constant consistent with zero order kinetics. In studies on a porcine cornea, the ability of CS to penetrate into the structure of the cornea was confirmed by determining the content of CS in the cornea after 5 minutes and 3 hours exposure to eye drops. The quality parameters of eye drops were assessed: pH, viscosity, osmolarity and microbiological purity. Stability tests were also performed on eye drops stored in unit minims packaging and in multi-dose bottle packaging. The following storage conditions were adopted: 40°C/75% RH, 25°C/60% RH, 2-8°C. The sensitivity of CS to light was also confirmed. The UV and HPLC-UV methods were used to assess the CS content, while the HPLC-UV and HPLC-MS/MS methods were used to assess the chromatographic purity.
Collapse
Affiliation(s)
- Katarzyna B Wróblewska
- Chair and Department of Pharmaceutical Technology, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznan, Poland
| | - Szymon Plewa
- Chair and Department of Inorganic and Analytical Chemistry, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznan, Poland
| | - Jolanta Długaszewska
- Chair and Department of Pharmaceutical Genetics and Microbiology, Poznan University of Medical Sciences, Święcickiego 6, 60-781 Poznan, Poland
| | - Anna Froelich
- Chair and Department of Pharmaceutical Technology, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznan, Poland
| | - Izabela Muszalska-Kolos
- Chair and Department of Pharmaceutical Chemistry, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznan, Poland.
| |
Collapse
|
|
33
|
Flitter BA, Fang X, Matthay MA, Gronert K. The potential of lipid mediator networks as ocular surface therapeutics and biomarkers. Ocul Surf 2021; 19:104-114. [PMID: 32360792 PMCID: PMC7606340 DOI: 10.1016/j.jtos.2020.04.008] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2019] [Revised: 04/10/2020] [Accepted: 04/12/2020] [Indexed: 01/03/2023]
Abstract
In the last twenty years an impressive body of evidence in diverse inflammatory animal disease models and human tissues, has established polyunsaturated fatty acids (PUFA) derived specialized-pro-resolving mediators (SPM), as essential mediators for controlling acute inflammation, immune responses, wound healing and for resolving acute inflammation in many non-ocular tissues. SPM pathways and receptors are highly expressed in the ocular surface where they regulate wound healing, nerve regeneration, innate immunity and sex-specific regulation of auto-immune responses. Recent evidence indicates that in the eye these resident SPM networks are important for maintaining ocular surface health and immune homeostasis. Here, we will review and discuss evidence for SPMs and other PUFA-derived mediators as important endogenous regulators, biomarkers for ocular surface health and disease and their therapeutic potential.
Collapse
Affiliation(s)
- Becca A Flitter
- School of Optometry, University of California Berkeley, Berkeley, CA, 94720, USA; Vision Science Program, University of California Berkeley, Berkeley, CA, 94720, USA
| | - Xiaohui Fang
- Department of Medicine and Anesthesia, University of California, San Francisco, CA, USA; Cardiovascular Research Institute, University of California, San Francisco, CA, USA
| | - Michael A Matthay
- Department of Medicine and Anesthesia, University of California, San Francisco, CA, USA; Cardiovascular Research Institute, University of California, San Francisco, CA, USA
| | - Karsten Gronert
- School of Optometry, University of California Berkeley, Berkeley, CA, 94720, USA; Vision Science Program, University of California Berkeley, Berkeley, CA, 94720, USA; Infectious Diseases and Immunity Program, University of California Berkeley, Berkeley, CA, 94720, USA.
| |
Collapse
|
|
34
|
Roberts JK, Meekins JM, Roush JK, Rankin AJ. Effects of topical instillation of 0.1% diclofenac sodium, 0.5% ketorolac tromethamine, and 0.03% flurbiprofen sodium on corneal sensitivity in ophthalmologically normal cats. Am J Vet Res 2020; 82:81-87. [PMID: 33369491 DOI: 10.2460/ajvr.82.1.81] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
OBJECTIVE To investigate the effects of short-term and prolonged topical instillation of 0.1% diclofenac sodium, 0.5% ketorolac tromethamine, and 0.03% flurbiprofen sodium on corneal sensitivity (CS) in ophthalmologically normal cats. ANIMALS 12 healthy adult domestic shorthair cats. PROCEDURES In the first of 2 study phases, each cat received 0.1% diclofenac sodium, 0.5% ketorolac tromethamine, 0.03% flurbiprofen sodium, and saline (0.9% NaCl; control) solutions (1 drop [0.05 mL]/eye, q 5 min for 5 treatments) in a randomized order with a 2-day washout period between treatments. For each cat, an esthesiometer was used to measure CS before treatment initiation (baseline) and at 15, 30, 45, and 60 minutes after the last dose. There was a 2-day washout period between phases. The second phase was similar to the first, except each treatment was administered at a dosage of 1 drop/eye, twice daily for 5 days and CS was measured before treatment initiation and at 15 minutes and 24 and 48 hours after the last dose. The Friedman test was used to evaluate change in CS over time. RESULTS None of the 4 treatments had a significant effect on CS over time in either study phase. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that neither short-term nor prolonged topical instillation of 3 NSAID ophthalmic solutions had any effect on the CS of healthy cats. Given potential differences in cyclooxygenase expression between healthy and diseased eyes, further investigation of the effects of topical NSAID instillation in the eyes of cats with ocular surface inflammation is warranted.
Collapse
|
|
35
|
Li H, Fan TJ, Zou P, Xu B. Diclofenac Sodium Triggers p53-Dependent Apoptosis in Human Corneal Epithelial Cells via ROS-Mediated Crosstalk. Chem Res Toxicol 2020; 34:70-79. [PMID: 33356180 DOI: 10.1021/acs.chemrestox.0c00319] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
Diclofenac sodium (DFS), a nonsteroidal anti-inflammatory drug, is frequently used in ophthalmology, but it causes negative effects on corneas. The mechanisms underlying the toxicities to corneas remains unclear. The present study was designed to assess the cytotoxicity of DFS to human corneal epithelial (HCEP) cells in vitro and further investigate its related mechanisms. The HCEP cells were treated with DFS at different concentrations ranging from 0.003 125% to 0.1%. DFS showed a dose- and time-dependent cytotoxicity to HCEP cells including abnormal morphology and declined viability. The 0.05% DFS-treated HCEP cells presented cell cycle arrest at S phase, reactive oxygen species (ROS) overproduction, and positive staining of phosphorylated H2AX, suggesting that DFS caused ROS-mediated DNA damage. The upregulation of p53 expression, formation of apoptotic body, phosphatidylserine externalization, and DNA ladder demonstrated that the p53-dependent apoptosis pathway was involved in the cytotoxicity of DFS. Furthermore, DFS activated caspase-8, caspase-9, and caspase-3 altered the expression levels of Bcl-2 family proteins including tBid, Bax, and Bcl-2, as well as increased poly(ADP-ribose) polymerase (PARP) cleavage. DFS also induced ΔΨm disruption, resulting in the release of cytochrome c and apoptosis-inducing factor into the cytoplasm. Additionally, the DFS-induced apoptosis was alleviated by p53 inhibitor. Taken together, DFS triggered p53-dependent apoptosis in HCEP cells via ROS-mediated crosstalk between the extrinsic and intrinsic pathways.
Collapse
Affiliation(s)
- Hui Li
- Laboratory for Corneal Tissue Engineering, College of Marine Life Sciences, Ocean University of China, Qingdao, Shandong 266100, China
| | - Ting-Jun Fan
- Laboratory for Corneal Tissue Engineering, College of Marine Life Sciences, Ocean University of China, Qingdao, Shandong 266100, China
| | - Ping Zou
- Marine Agriculture Research Center, Tobacco Research Institute of Chinese Academy of Agricultural Sciences, Qingdao, Shandong 266101, China
| | - Bin Xu
- Laboratory for Corneal Tissue Engineering, College of Marine Life Sciences, Ocean University of China, Qingdao, Shandong 266100, China
| |
Collapse
|
|
36
|
Moon CW, Park DG, Sagong M. Effect of Topical Bromfenac as a Treatment of Cystoid Macular Edema Following Pars Plana Vitrectomy. JOURNAL OF THE KOREAN OPHTHALMOLOGICAL SOCIETY 2020. [DOI: 10.3341/jkos.2020.61.12.1467] [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]
|
|
37
|
Heard CM. An ex vivo skin model to probe modulation of local cutaneous arachidonic acid inflammation pathway. J Biol Methods 2020; 7:e138. [PMID: 33204741 PMCID: PMC7666330 DOI: 10.14440/jbm.2020.319] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2019] [Revised: 05/15/2020] [Accepted: 05/17/2020] [Indexed: 02/02/2023] Open
Abstract
There is a need for inexpensive and reliable means to determine the modulation of cutaneous inflammation. The method outlined in this article draws together a number of scientific techniques and makes use of generally unwanted biological tissues as a means of determining skin inflammation ex vivo, and focuses on probing aspects of the arachidonic acid inflammation pathway. Freshly excised skin contains elevated levels of short-lived inducible cyclooxygenase-2 (COX-2) and, under viable conditions, COX-2 and its eicosanoid products will continue to be produced until tissue necrosis, providing a window of time in which relative levels can be probed to determine exacerbation due to an upregulating factor or downregulation due the presence of an agent exerting anti-inflammatory activity. Ex vivo porcine skin, mounted in Franz diffusion cells, is dosed topically with the xenobiotic challenge and then techniques such as Western blotting and immunohistochemistry can then be used to probe relative COX-2 levels on a semi-quantitative or qualitative level. Enzyme-linked immunosorbent assay or LCMS can be used to determine relative prostaglandin E-2 (PGE-2) levels. Thus far, the technique has been used to examine the effects of topically applied anti-inflammatories (betamethasone, ibuprofen, ketoprofen and methotrexate), natural products (fish oil, Devil’s claw extract and pomegranate rind extract) and drug delivery vehicle (polyNIPAM nanogels). Topically applied xenobiotics that modulate factors such as COX-2 and PGE-2 must penetrate the intact skin, and this provides direct evidence of overcoming the "barrier function" of the stratum corneum in order to target the viable epidermis in sufficient levels to be able to elicit such effects. This system has particular potential as a pre-clinical screening tool for those working on the development of topical delivery systems, and has the additional advantage of being in line with 3 Rs philosophy.
Collapse
Affiliation(s)
- Charles M Heard
- School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff CF10 3 NB Wales, United Kingdom
| |
Collapse
|
|
38
|
Razumova IY, Godzenko AA. [Nonsteroidal anti-inflammatory drugs in the treatment of anterior uveitis associated with spondyloarthritis]. Vestn Oftalmol 2020; 136:70-77. [PMID: 33084282 DOI: 10.17116/oftalma202013606170] [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: 11/17/2022]
Abstract
Anterior uveitis (AU) is one of the common extraskeletal manifestations of spondyloarthritis (SpA). The course of AU in patients with SpA is characterized by frequent relapses. The article considers the question of local and systemic use of nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment and prevention of SpA-associated uveitis exacerbations.
Collapse
Affiliation(s)
| | - A A Godzenko
- Russian Medical Academy of Continuous Professional Education, Moscow, Russia
| |
Collapse
|
|
39
|
Kendre PN, Kadam PD, Jain SP, Vibhute SK, Pote AK. Design, fabrication, and characterization of graft co-polymer assisted ocular insert: a state of art in reducing post-operative pain. Drug Dev Ind Pharm 2020; 46:1988-1999. [PMID: 33026260 DOI: 10.1080/03639045.2020.1833908] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
PURPOSE Targeted delivery of drugs at appropriate concentrations to ocular tissues is required to avoid wastage. Hence, advanced systems that maximize the release of poorly soluble drugs and deliver them at ocular sites must be designed. METHODS In this study, Soluplus® (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol-graft copolymer) was selected as a solubilizer as well as film former for preparing ocular inserts and polyethylene glycol 400 (PEG-400) as a plasticizer. On the basis of an initial phase solubility study, the maximum concentration of Soluplus® possible was used for developing the inserts. An optimized formulation was obtained using a 32-factorial design. Two factors at three levels were used to design the ocular inserts. Soluplus® (X 1) and the plasticizer, PEG-400 (X 2), were set as the independent variables at various levels, and the Rel4h (drug release in 4 h, Y 1) and tensile strength (Y 2) were set as the dependent variables. A pre-formulation study was conducted to select suitable materials. RESULTS Various physico-chemical parameters of the optimized formulation, including the tensile strength and folding endurance, were studied using FT-IR, DSC, XRD, and SEM. An in vitro dissolution study was conducted to determine the amount of drug released. There was no redness, swelling, or watering of the rabbit eye. CONCLUSION It was concluded that the ocular inserts of the poorly soluble nepafenac developed using a graft-co-polymer enhanced the solubility and utilization of the drug for a prolonged period.
Collapse
Affiliation(s)
- Prakash N Kendre
- Department of Pharmaceutics, Rajarshi Shahu College of Pharmacy, Buldana, India
| | - Pooja D Kadam
- Department of Pharmaceutics, Sanjivani College of Pharmaceutical Education & Research, Kopargaon, India
| | | | - Somnath K Vibhute
- Department of Pharmaceutics, Rajarshi Shahu College of Pharmacy, Buldana, India
| | - Ajinkya K Pote
- Department of Pharmaceutics, Rajarshi Shahu College of Pharmacy, Buldana, India
| |
Collapse
|
|
40
|
Khan SA, Lee CS. Recent progress and strategies to develop antimicrobial contact lenses and lens cases for different types of microbial keratitis. Acta Biomater 2020; 113:101-118. [PMID: 32622052 DOI: 10.1016/j.actbio.2020.06.039] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2020] [Revised: 06/24/2020] [Accepted: 06/25/2020] [Indexed: 12/16/2022]
Abstract
Although contact lenses are widely used for vision correction, they are also the primary cause of a number of ocular diseases such as microbial keratitis (MK), etc. and inflammatory events such as infiltrative keratitis (IK), contact lens acute red eye (CLARE), contact lens-induced peripheral ulcer (CLPU), etc. These diseases and infiltrative events often result from microbial contamination of lens care solutions and lens cases that can be exacerbated by unsanitary lens care and extended lens wear. The treatment of microbial biofilms (MBs) on lens cases and contact lenses are complicated and challenging due to their resistance to conventional antimicrobial lens care solutions. More importantly, MK caused by MBs can lead to acute visual damage or even vision impairment. Therefore, the development of lens cases, lens care solutions, and contact lenses with effective antimicrobial performance against MK will contribute to the safe use of contact lenses. This review article summarizes and discusses different chemical approaches for the development of antimicrobial contact lenses and lens cases employing passive surface modifications, antimicrobial peptides, free-radical fabricating agents, quorum sensing quenchers, antibiotics, antifungal drugs and various metals and coatings with antimicrobial nanomaterials. The benefits and shortcomings of these approaches are assessed, and alternative solutions for future developments are discussed.
Collapse
Affiliation(s)
- Shakeel Ahmad Khan
- Center of Super-Diamond and Advanced Films (COSDAF), Department of Chemistry, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong
| | - Chun-Sing Lee
- Center of Super-Diamond and Advanced Films (COSDAF), Department of Chemistry, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong.
| |
Collapse
|
|
41
|
Kiziltoprak H, Koc M, Yetkin E, Tekin K, Inanc M, Ozulken K. Additive Effect of Topical Nepafenac on Mydriasis in Patients With Diabetes Mellitus. Eye Contact Lens 2020; 46:310-313. [PMID: 31503086 DOI: 10.1097/icl.0000000000000657] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVES To evaluate the additive effect of topical nepafenac on pupil diameter (PD) in patients with diabetes mellitus (DM) and cataract. METHODS This prospective comparative study included the patients having cataract surgery with and without DM. Two consecutive PD measurements were taken using an automatic quantitative pupillometry system (MonPack One, Metrovision). A baseline measurement was taken, then one drop of nepafenac % 0.1 (Nevanac; Alcon, Fort Worth, TX) was instilled only to the eye that will be operated on (study eye). Cyclopentolate 1.0% (Sikloplejin; Abdi İbrahim, İstanbul, Turkey) was instilled to both eyes (study eye/fellow eye) 5 minutes later. The second measurement was taken at 1 hour after this application. RESULTS The DM group consisted of 43 patients, and the control group consisted of 39 participants. The baseline PDs of both eyes were similar in the DM group (P=0.070) and the control group (P=0.345). The change in pupil size from baseline to mydriasis was statistically significantly greater in the study eyes (2.69±0.53) than fellow eyes (2.54±0.61) in the DM group (P=0.009), but there was no statistically significant difference in the control group (2.94±0.63 vs. 2.86±0.58). When the groups were compared, the PD changes were similar in the study eyes between groups (P=0.065), while the PD changes in the fellow eyes were lower in the DM group (P=0.017). CONCLUSIONS Nepafenac has been shown additive effect on pupil dilation in diabetic patients before cataract surgery.
Collapse
Affiliation(s)
- Hasan Kiziltoprak
- Ophthalmology Department (H.K.), Bingol Women's Health and Children's Hospital, Bingol, Turkey; Ophthalmology Department (M.K., E.Y.), Ankara Ulucanlar Eye Training and Research Hospital, Ankara, Turkey; Ophthalmology Department (K.T., M.I.), Ercis State Hospital, Van, Turkey; and Ophthalmology Department (K.O.), TOBB ETU Hospital, Ankara, Turkey
| | | | | | | | | | | |
Collapse
|
|
42
|
Beharry KD, Cai CL, Siddiqui F, D’Agrosa C, Zangaladze A, Mustafa G, Qadri A, Duggan TJ, Aranda JV. Combination Antioxidant/NSAID Therapies and Oral/Topical Ocular Delivery Modes for Prevention of Oxygen-Induced Retinopathy in a Rat Model. Nutrients 2020; 12:nu12071980. [PMID: 32635350 PMCID: PMC7400869 DOI: 10.3390/nu12071980] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Revised: 06/26/2020] [Accepted: 06/30/2020] [Indexed: 11/17/2022] Open
Abstract
Given the complexity of oxygen-induced retinopathy (OIR), we tested the hypothesis that combination therapies and modes of administration would synergistically optimize efficacy for prevention of OIR. Newborn rats were exposed to neonatal intermittent hypoxia (IH) from the first day of life (P0) until P14 during which they received: (1) oral glutathione nanoparticles (nGSH) with topical ocular phosphate buffered saline (PBS); (2) nGSH with topical ocular Acuvail (ACV); (3) oral coenzyme Q10 (CoQ10) + ACV; (4) oral omega 3 polyunsaturated fatty acids (n-3 PUFAs) + ACV; (5) CoQ10 + n-3 PUFAs + PBS; or (6) CoQ10 + n-3 PUFAs + ACV. Treated groups raised in room air (RA) served as controls. At P14, pups were placed in RA with no treatment until P21. Retinal vascular pathology, ocular angiogenesis biomarkers, histopathology, and morphometry were determined. All combination treatments in IH resulted in the most beneficial retinal outcomes consistent with suppression of angiogenesis growth factors during reoxygenation/reperfusion and no significant adverse effects on somatic growth. nGSH + PBS also reversed IH-induced retinopathy, but had negative effects on growth. Simultaneously targeting oxidants, inflammation, and poor growth mitigates the damaging effects of neonatal IH on the developing retina. Therapeutic synergy with combination delivery methods enhance individual attributes and simultaneously target multiple pathways involved in complex diseases such as OIR.
Collapse
Affiliation(s)
- Kay D. Beharry
- Division of Neonatal-Perinatal Medicine, Department of Pediatrics, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA; (C.L.C.); (F.S.); (A.Z.); (G.M.); (A.Q.); (T.J.D.); (J.V.A.)
- Department of Ophthalmology, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA
- SUNY Eye Institute, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA
- Correspondence: ; Tel.: +01-718-270-1475
| | - Charles L. Cai
- Division of Neonatal-Perinatal Medicine, Department of Pediatrics, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA; (C.L.C.); (F.S.); (A.Z.); (G.M.); (A.Q.); (T.J.D.); (J.V.A.)
| | - Faisal Siddiqui
- Division of Neonatal-Perinatal Medicine, Department of Pediatrics, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA; (C.L.C.); (F.S.); (A.Z.); (G.M.); (A.Q.); (T.J.D.); (J.V.A.)
| | - Christina D’Agrosa
- Division of Neonatal-Perinatal Medicine, Department of Pediatrics, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA; (C.L.C.); (F.S.); (A.Z.); (G.M.); (A.Q.); (T.J.D.); (J.V.A.)
| | - Anano Zangaladze
- Division of Neonatal-Perinatal Medicine, Department of Pediatrics, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA; (C.L.C.); (F.S.); (A.Z.); (G.M.); (A.Q.); (T.J.D.); (J.V.A.)
| | - Ghassan Mustafa
- Division of Neonatal-Perinatal Medicine, Department of Pediatrics, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA; (C.L.C.); (F.S.); (A.Z.); (G.M.); (A.Q.); (T.J.D.); (J.V.A.)
| | - Areej Qadri
- Division of Neonatal-Perinatal Medicine, Department of Pediatrics, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA; (C.L.C.); (F.S.); (A.Z.); (G.M.); (A.Q.); (T.J.D.); (J.V.A.)
| | - Thomas J. Duggan
- Division of Neonatal-Perinatal Medicine, Department of Pediatrics, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA; (C.L.C.); (F.S.); (A.Z.); (G.M.); (A.Q.); (T.J.D.); (J.V.A.)
| | - Jacob V. Aranda
- Division of Neonatal-Perinatal Medicine, Department of Pediatrics, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA; (C.L.C.); (F.S.); (A.Z.); (G.M.); (A.Q.); (T.J.D.); (J.V.A.)
- Department of Ophthalmology, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA
- SUNY Eye Institute, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA
| |
Collapse
|
|
43
|
Mazet R, Yaméogo JBG, Wouessidjewe D, Choisnard L, Gèze A. Recent Advances in the Design of Topical Ophthalmic Delivery Systems in the Treatment of Ocular Surface Inflammation and Their Biopharmaceutical Evaluation. Pharmaceutics 2020; 12:pharmaceutics12060570. [PMID: 32575411 PMCID: PMC7356360 DOI: 10.3390/pharmaceutics12060570] [Citation(s) in RCA: 62] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Revised: 06/06/2020] [Accepted: 06/09/2020] [Indexed: 12/17/2022] Open
Abstract
Ocular inflammation is one of the most common symptom of eye disorders and diseases. The therapeutic management of this inflammation must be rapid and effective in order to avoid deleterious effects for the eye and the vision. Steroidal (SAID) and non-steroidal (NSAID) anti-inflammatory drugs and immunosuppressive agents have been shown to be effective in treating inflammation of the ocular surface of the eye by topical administration. However, it is well established that the anatomical and physiological ocular barriers are limiting factors for drug penetration. In addition, such drugs are generally characterized by a very low aqueous solubility, resulting in low bioavailability as only 1% to 5% of the applied drug permeates the cornea. The present review gives an updated insight on the conventional formulations used in the treatment of ocular inflammation, i.e., ointments, eye drops, solutions, suspensions, gels, and emulsions, based on the commercial products available on the US, European, and French markets. Additionally, sophisticated formulations and innovative ocular drug delivery systems will be discussed. Promising results are presented with micro- and nanoparticulated systems, or combined strategies with polymers and colloidal systems, which offer a synergy in bioavailability and sustained release. Finally, different tools allowing the physical characterization of all these delivery systems, as well as in vitro, ex vivo, and in vivo evaluations, will be considered with regards to the safety, the tolerance, and the efficiency of the drug products.
Collapse
Affiliation(s)
- Roseline Mazet
- DPM, UMR CNRS 5063, ICMG FR 2607, Faculty of Pharmacy, University of Grenoble Alpes, 38400 St Martin d’Hères, France; (R.M.); (D.W.); (L.C.)
- Grenoble University Hospital, 38043 Grenoble, France
| | | | - Denis Wouessidjewe
- DPM, UMR CNRS 5063, ICMG FR 2607, Faculty of Pharmacy, University of Grenoble Alpes, 38400 St Martin d’Hères, France; (R.M.); (D.W.); (L.C.)
| | - Luc Choisnard
- DPM, UMR CNRS 5063, ICMG FR 2607, Faculty of Pharmacy, University of Grenoble Alpes, 38400 St Martin d’Hères, France; (R.M.); (D.W.); (L.C.)
| | - Annabelle Gèze
- DPM, UMR CNRS 5063, ICMG FR 2607, Faculty of Pharmacy, University of Grenoble Alpes, 38400 St Martin d’Hères, France; (R.M.); (D.W.); (L.C.)
- Correspondence: ; Tel.: +33-476-63-53-01
| |
Collapse
|
|
44
|
Işık MU, Yalçındağ NF. Comparison of the efficacy of nepafenac 0.1% in quiescent Behçet's uveitis and non-uveitic healthy patients after phacoemulsification surgery. Int Ophthalmol 2020; 40:2345-2351. [PMID: 32419106 DOI: 10.1007/s10792-020-01419-z] [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: 04/05/2020] [Accepted: 05/05/2020] [Indexed: 11/26/2022]
Abstract
PURPOSE To compare the efficacy of nepafenac on anterior chamber flare and intraocular pressure(IOP) in healthy (group 1) and uveitic eyes (group 2) undergoing cataract surgery. METHODS A retrospective, consecutive case series study. RESULTS Among 54 the patients, 14 had a history of uveitis. The groups were similar in age and gender. There were significant changes in flare values in both groups. When the temporal changes of flare values were compared, there was no difference between the two groups. There were no significant changes in IOP values in both group. When the temporal changes of IOP values were compared, there was no difference between the groups. CONCLUSIONS Nepafenac 0.1% has been shown to be effective in suppressing inflammation after cataract surgery in uveitic eyes as well as in healthy eyes. In addition, it has been observed that it does not increase intraocular pressure in both healthy and uveitic eyes and it is safe to use with this regard.
Collapse
Affiliation(s)
- Mehmed Uğur Işık
- Ophthalmology Department, Balıklıgöl State Hospital, Sanliurfa, Turkey.
| | | |
Collapse
|
|
45
|
Kandarakis SA, Petrou P, Papakonstantinou E, Spiropoulos D, Rapanou A, Georgalas I. Ocular nonsteroidal inflammatory drugs: where do we stand today? Cutan Ocul Toxicol 2020; 39:200-212. [PMID: 32338073 DOI: 10.1080/15569527.2020.1760876] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Since their first introduction in ophthalmology, the use of NSAIDs (nonsteroidal anti-inflammatory drugs) has been exponentially expanded, with numerous therapeutic applications. Despite their controversial history, they have proven their efficacy as anti-inflammatory agents in a variety of diseases. Nowadays, NSAIDs are part of surgical protocols of the most commonly performed ophthalmic operations, such as cataract or ocular surgery. They are universally implicated in the management of conjunctivitis, retinal and choroidal disease and miscellaneous inflammatory diseases. Moreover, although linked with serious adverse events and toxicities, their therapeutic magnitude in Ophthalmology should not be affected. This review systematically portrays the variety of ocular NSAIDs available to date, along with their differences in their way of action, indications and potential side effects in various ophthalmologic conditions.
Collapse
Affiliation(s)
- S A Kandarakis
- Department of Ophthalmology, National and Kapodistrian University of Athens, 1st University Eye Clinic, G. Gennimatas General Hospital, Athens, Greece
| | - P Petrou
- Department of Ophthalmology, National and Kapodistrian University of Athens, 1st University Eye Clinic, G. Gennimatas General Hospital, Athens, Greece
| | - E Papakonstantinou
- Department of Ophthalmology, National and Kapodistrian University of Athens, 1st University Eye Clinic, G. Gennimatas General Hospital, Athens, Greece
| | - D Spiropoulos
- Department of Ophthalmology, National and Kapodistrian University of Athens, 1st University Eye Clinic, G. Gennimatas General Hospital, Athens, Greece
| | - A Rapanou
- Department of Ophthalmology, National and Kapodistrian University of Athens, 1st University Eye Clinic, G. Gennimatas General Hospital, Athens, Greece
| | - I Georgalas
- Department of Ophthalmology, National and Kapodistrian University of Athens, 1st University Eye Clinic, G. Gennimatas General Hospital, Athens, Greece
| |
Collapse
|
|
46
|
The Therapeutic Effects and Possible Mechanism of Pranoprofen in Mouse Model of Corneal Alkali Burns. J Ophthalmol 2020; 2020:7485912. [PMID: 32322412 PMCID: PMC7166258 DOI: 10.1155/2020/7485912] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2019] [Revised: 02/12/2020] [Accepted: 03/09/2020] [Indexed: 11/17/2022] Open
Abstract
Objective To investigate therapeutic effects and possible mechanism of pranoprofen in a mouse model of corneal alkali burns and provide new evidence for the clinical treatment of corneal alkali burns. Methods A unilateral alkali burn was created in the central cornea by placing a piece of 2 mm diameter filter paper soaked in 1N NaOH on the right eye for 30 seconds. After the model was performed, C57BL/6J mice received topical treatment with saline eye drops or pranoprofen eye drops and were, respectively, categorized as saline group and pranoprofen group, whereas the remaining normal mice that were not subjected to alkali burns served as control, each group containing 15 mice (n = 45). On the 5th day after model establishment, the corneal fluorescein sodium staining score was evaluated in order to assess corneal epithelial damage. Tissue HE stain was used to observe the pathological changes of corneal tissue in each group. Real-time RT-PCR and western blot were also performed to detect the mRNA and protein expression of NLRP3, IL-1β/p17, and matrix metallopeptidase MMP-13. Results 5 days after burns, microscopic observations of the pranoprofen group showed less corneal opacity and neovascularization development than the saline group. Sodium fluorescein staining showed obvious corneal structure disorders, poor corneal epithelium continuity, and a larger corneal epithelial defect area in the saline group (10.33±+−0.57) as opposed to the pranoprofen group (8.33 ± 0.57） (p < 0.05). HE stain results showed the saline group had obvious corneal structure disorder and the corneal epithelial layer was incomplete as opposed to the pranoprofen group. PCR and western blot results suggested that the pranoprofen group expressed less NLRP3, IL-1β, and MMP-13 mRNA and protein expression in corneal tissue than the saline group (p < 0.05). Conclusion Pranoprofen may alleviate inflammatory response by inhibiting the expression levels of NLRP3 and IL-1β at the early stage of corneal alkali injury, lowering the expression of MMP-13 and ultimately reducing corneal epithelial damage.
Collapse
|
|
47
|
Toro MD, Nowakowska D, Brzozowska A, Reibaldi M, Avitabile T, Bucolo C, Murabito P, Chisari C, Nowomiejska K, Rejdak R. Pain Following the Use of Anesthesia Formulation Among Individuals Undergoing Cataract Surgery: A Randomized Controlled Trial. Front Pharmacol 2020; 11:440. [PMID: 32372954 PMCID: PMC7176993 DOI: 10.3389/fphar.2020.00440] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2019] [Accepted: 03/20/2020] [Indexed: 11/24/2022] Open
Abstract
Purpose To assess the pain intensity of two intracameral anesthetic solutions in patients undergoing cataract surgery and evaluate the factors influencing the patients’ postoperative activities. Methods Sixty-two patients undergoing cataract surgery were randomized to receive the study drug – a manufactured solution of 0.02% tropicamide/0.31% phenylephrine/1% lidocaine (Mydrane) or a traditional anesthetic formulation - solution of 1% lidocaine/0.025% adrenaline as an intraocular anesthetic. The pain intensity was assessed by Visual Analog Scale for Pain (VAS Pain) and Brief Pain Inventory-short form (BPI) on the next day after the surgery. Results The mean pain score measured preoperatively with VAS Pain was 0.34 in Mydrane group and 0.09 in the reference group (p = 0.51). There were no statistically significant differences between the two anesthetic methods with respect to pain intensity during the surgery (p = 0.94) and the influence of pain during the last 24 h on activity (p = 0.79), mood (p = 0.31), social contacts (p = 0.29), sleep (p = 0.5) and the joy of life (p = 0.39). Additionally, there was no statistically significant influence of age, sex, lateralization, co-existing ophthalmological diseases (p = 0.98) and post-operative complications (p = 0.4) on the experienced pain measured during the surgery and in the last 24 h. Conclusions New commercially available intraocular anesthetic solution (Mydrane™) seems to be as effective as off-label traditional anesthetic formulation, in reducing the pain experienced during cataract surgery under topical anesthesia.
Collapse
Affiliation(s)
- Mario D Toro
- Department of General Ophthalmology, Medical University of Lublin, Lublin, Poland.,Faculty of Medicine, Collegium Medicum, Cardinal Stefan Wyszynski University, Warsaw, Poland
| | - Dominika Nowakowska
- Department of General Ophthalmology, Medical University of Lublin, Lublin, Poland
| | - Agnieszka Brzozowska
- Department of Mathematics and Medical Biostatistics, Medical University of Lublin, Lublin, Poland
| | - Michele Reibaldi
- Department of Ophthalmology, School of Medicine, University of Catania, Catania, Italy
| | - Teresio Avitabile
- Department of Ophthalmology, School of Medicine, University of Catania, Catania, Italy
| | - Claudio Bucolo
- Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania, Italy
| | - Paolo Murabito
- Department of General Surgery and Surgical Specialties, Division of Anesthesiology, Azienda Ospedaliero-Universitaria Policlinico, Catania, Italy
| | - Clara Chisari
- Department "GF. Ingrassia", Section of Neurosciences, University of Catania, Catania, Italy
| | | | - Robert Rejdak
- Department of General Ophthalmology, Medical University of Lublin, Lublin, Poland
| |
Collapse
|
|
48
|
Li F, Wen Y, Zhang Y, Zheng K, Ban J, Xie Q, Wen Y, Liu Q, Chen F, Mo Z, Liu L, Chen Y, Lu Z. Characterisation of 2-HP-β-cyclodextrin-PLGA nanoparticle complexes for potential use as ocular drug delivery vehicles. ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY 2020; 47:4097-4108. [PMID: 31663388 DOI: 10.1080/21691401.2019.1683567] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Aim: 2-HP-β-cyclodextrin-PLGA nanoparticle complexes were prepared to enhance the aqueous humour delivery of Triamcinolone acetonide.Materials & methods: Drug-loaded 2-HP-β-CD/PLGA nanoparticle complexes prepared by adapting a quasi-emulsion solvent evaporation technique. In vitro drug release, in vitro transcorneal permeation study, histopathological study and in vivo transcorneal penetration of PLGA nanoparticles and 2-HP-β-CD/PLGA nanoparticle complexes were evaluated. Results: Particle size distributions of 2-HP-β-CD/PLGA nanoparticle complexes were 149.4 ± 3.7 nm and presented stable system. Corneal penetration studies revealed steady sustained drug release (First-order); 2-HP-β-CD/PLGA nanoparticle complexes increased ocular bioavailability by increasing dispersion in the tear film and improving drug release. Conclusion: 2-HP-β-CD/PLGA nanoparticle complex formulation is a promising alternative to conventional eye drops.
Collapse
Affiliation(s)
- Fan Li
- Guangdong Provincial Key Laboratory of Advanced Drug Delivery Systems, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China.,Guangdong Provincial Engineering Center of Topical Precise Drug Delivery Systems, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China.,R&D Team for Formulation Innovation, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China
| | - Yuqin Wen
- Guangdong Provincial Key Laboratory of Advanced Drug Delivery Systems, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China.,Guangdong Provincial Engineering Center of Topical Precise Drug Delivery Systems, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China.,R&D Team for Formulation Innovation, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China
| | - Yan Zhang
- Guangdong Provincial Key Laboratory of Advanced Drug Delivery Systems, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China.,Guangdong Provincial Engineering Center of Topical Precise Drug Delivery Systems, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China.,R&D Team for Formulation Innovation, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China
| | - Kangyu Zheng
- Guangdong Provincial Key Laboratory of Advanced Drug Delivery Systems, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China.,Guangdong Provincial Engineering Center of Topical Precise Drug Delivery Systems, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China.,R&D Team for Formulation Innovation, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China
| | - Junfeng Ban
- Guangdong Provincial Key Laboratory of Advanced Drug Delivery Systems, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China.,Guangdong Provincial Engineering Center of Topical Precise Drug Delivery Systems, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China.,R&D Team for Formulation Innovation, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China
| | - Qingchun Xie
- Guangdong Provincial Key Laboratory of Advanced Drug Delivery Systems, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China.,Guangdong Provincial Engineering Center of Topical Precise Drug Delivery Systems, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China.,R&D Team for Formulation Innovation, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China
| | - Yifeng Wen
- Guangdong Provincial Key Laboratory of Advanced Drug Delivery Systems, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China.,Guangdong Provincial Engineering Center of Topical Precise Drug Delivery Systems, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China.,R&D Team for Formulation Innovation, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China
| | - Qing Liu
- Guangdong Provincial Key Laboratory of Advanced Drug Delivery Systems, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China.,Guangdong Provincial Engineering Center of Topical Precise Drug Delivery Systems, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China.,R&D Team for Formulation Innovation, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China
| | - Fohua Chen
- Guangdong Provincial Key Laboratory of Advanced Drug Delivery Systems, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China.,Guangdong Provincial Engineering Center of Topical Precise Drug Delivery Systems, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China.,R&D Team for Formulation Innovation, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China
| | - Zhenjie Mo
- Guangdong Provincial Key Laboratory of Advanced Drug Delivery Systems, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China.,Guangdong Provincial Engineering Center of Topical Precise Drug Delivery Systems, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China.,R&D Team for Formulation Innovation, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China
| | - Lizhong Liu
- Department of Hospital Pharmacy, Ningbo 7 Hospital, Ningbo, People's Republic of China
| | - Yanzhong Chen
- Guangdong Provincial Key Laboratory of Advanced Drug Delivery Systems, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China.,Guangdong Provincial Engineering Center of Topical Precise Drug Delivery Systems, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China.,R&D Team for Formulation Innovation, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China
| | - Zhufen Lu
- Guangdong Provincial Key Laboratory of Advanced Drug Delivery Systems, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China.,Guangdong Provincial Engineering Center of Topical Precise Drug Delivery Systems, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China.,R&D Team for Formulation Innovation, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China
| |
Collapse
|
|
49
|
Song SH, Baek SK, Lee MW, Lee YH. Effect of 0.1% Bromfenac for Preventing Macular Edema after Cataract Surgery in Patients with Diabetes. KOREAN JOURNAL OF OPHTHALMOLOGY 2020; 34:46-55. [PMID: 32037749 PMCID: PMC7010466 DOI: 10.3341/kjo.2019.0044] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2019] [Revised: 09/30/2019] [Accepted: 10/08/2019] [Indexed: 12/03/2022] Open
Abstract
Purpose To investigate the effect of 0.1% bromfenac sodium hydrate ophthalmic solution for prevention of macular edema after cataract surgery in patients with diabetes. Methods A retrospective analysis of 75 patients with diabetes who underwent cataract surgery was performed. Thirty-eight patients (52 eyes) were instilled with 0.1% bromfenac solution (bromfenac group) and 37 patients (46 eyes) were not (control group). Results There were no significant preoperative between-group differences. Compared to the control group, at 1 month after surgery, the bromfenac group showed slightly better best-corrected visual acuity (0.12 ± 0.12 vs. 0.32 ± 0.42, p = 0.142), lower central macular thickness (265.58 ± 31.28 vs. 314.15 ± 76.11 µm, p < 0.001), and lower macular volume (8.46 ± 0.60 vs. 9.14 ± 1.53 mm3, p = 0.022). There were no significant differences between the two groups at 4 and 6 months postoperatively (p > 0.05). Mean changes in central macular thickness showed significant differences at 1 and 4 months postoperatively (−1.44 ± 11.72 and 10.44 ± 22.48 µm in bromfenac group vs. 47.19 ± 70.24 and 31.69 ± 48.04 µm in control group, p < 0.001 and p = 0.016) and mean changes in macular volume showed a significant difference at 1 month postoperatively (−0.08 ± 0.47 mm3 in bromfenac group vs. 0.58 ± 1.28 mm3 in control group, p < 0.001). There were no significant differences thereafter (p > 0.05). Conclusions Treatment with 0.1% bromfenac sodium hydrate ophthalmic solution showed good efficacy for preventing cystoid macular edema early after cataract surgery in patients with diabetes.
Collapse
Affiliation(s)
- Seok Hyeon Song
- Department of Ophthalmology, Konyang University College of Medicine, Daejeon, Korea
| | - Seung Kook Baek
- Department of Ophthalmology, Konyang University College of Medicine, Daejeon, Korea
| | - Min Woo Lee
- Department of Ophthalmology, Konyang University College of Medicine, Daejeon, Korea
| | - Young Hoon Lee
- Department of Ophthalmology, Konyang University College of Medicine, Daejeon, Korea.
| |
Collapse
|
|
50
|
Rathod VR, Shah DA, Dave RH. Systematic implementation of quality-by-design (QbD) to develop NSAID-loaded nanostructured lipid carriers for ocular application: preformulation screening studies and statistical hybrid-design for optimization of variables. Drug Dev Ind Pharm 2020; 46:443-455. [DOI: 10.1080/03639045.2020.1724135] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Affiliation(s)
- Vishal R. Rathod
- Department of Pharmaceutical Sciences, Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, NY, USA
| | | | - Rutesh H. Dave
- Department of Pharmaceutical Sciences, Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, NY, USA
| |
Collapse
|