Purpose: Repeated intravitreal injections of methotrexate for proliferative vitreoretinopathy, a rare ocular condition that can cause vision loss, have shown beneficial effects in recent clinical studies. The purpose of this study was to develop a slow-release, long-term drug carrier composed of the polymer polylactide-co-glycolide and methotrexate that can be injected intravitreally.
Methods: The required composition of the drug carrier was modeled using pharmacokinetic parameters based on current literature. Release kinetics were determined using an ocular pharmacokinetic model. Epiretinal PVR-membranes were harvested during pars plana vitrectomy and subsequently transferred to cell culture. The effect of the drug carrier on cell migration was investigated using time-lapse microscopy and a scratch-induced migration assay. The colorimetric WST-1-assay and a live-dead-assay were performed to determine viability, and the BrdU-assay was applied for proliferation.
Results: The release profile showed an initial and a final burst of methotrexate with an intervening steady state that lasted 9-11 weeks. It showed inhibitory effects on pathobiological processes in human PVR-cells in vitro. Cell velocity in the time-lapse assay, migration in the scratch assay (p = 0.001), and proliferation in the BrdU assay (p = 0.027) were reduced after addition of the drug carrier. These effects occurred without causing a reduction in viability in the WST-1 assay (p > 0.99) and the live-dead assay.
Conclusion: The methotrexate-loaded drug carrier can maintain a stable concentration for 9-11 weeks and influence the pathobiological process of PVR cells in vitro. Therefore, it represents a potential therapeutic orphan drug for PVR.
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http://dx.doi.org/10.1016/j.biopha.2022.114088 | DOI Listing |
Inflammopharmacology
December 2024
Riphah Institute of Pharmaceutical Sciences, Riphah International University, Lahore Campus, Lahore, 5400, Pakistan.
Rheumatoid arthritis is an autoimmune disorder affecting multiple joints and requires lifelong treatment. Present study was designed to formulate Esculin-loaded chitosan nanoparticles (ENPs) and evaluation of its anti-inflammatory and anti-arthritic action. The acute toxicity study of ENPs was also performed.
View Article and Find Full Text PDFParasit Vectors
December 2024
Department of Medical Parasitology and Mycology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
Background: Cystic echinococcosis (CE) is a common neglected parasitic disease. Nanoparticles containing drugs have been widely utilized in various formulations for several purposes, including improving the bioavailability of drugs by increasing the solubility and dissolution rate of the nanoparticles. The purpose of this study was to evaluate the effects of solid lipid nanoparticles containing albendazole and conjugated to albumin (B-SLN + ABZ) as a novel treatment approach for hydatid cysts in vivo.
View Article and Find Full Text PDFJ Nanobiotechnology
December 2024
Key Laboratory of Special Environmental Medicine of Xinjiang, General Hospital of Xinjiang Military Command, No. 359, Youhao North Road, Urumqi, Xinjiang, China.
Objective: This study aims to elucidate the mechanisms by which nanovesicles (NVs) transport curcumin(CUR) across the blood-brain barrier to treat hypothalamic neural damage induced by heat stroke by regulating the expression of poly(c)-binding protein 2 (PCBP2).
Methods: Initially, NVs were prepared from macrophages using a continuous extrusion method. Subsequently, CUR was loaded into NVs using sonication, yielding engineered cell membrane Nanovesicles loaded with curcumin (NVs-CUR), which were characterized and subjected to in vitro and in vivo tracking analysis.
Sci Rep
December 2024
Department of Biomedical Sciences, College of Health Sciences, Qatar University, PO Box 2713, Doha, Qatar.
Diabetes mellitus is a chronic disease characterized by metabolic defects, including insulin deficiency and resistance. Individuals with diabetes are at increased risk of developing cardiovascular complications, such as atherosclerosis, coronary artery disease, and hypertension. Conventional treatment methods, though effective, are often challenging, costly, and may lead to systemic side effects.
View Article and Find Full Text PDFSci Rep
December 2024
Department of Pharmaceutics, Faculty of Pharmacy, Mazandaran University of Medical Sciences, PO Box. 48175-1665, Sari, Iran.
Luliconazole (LCZ) is a topical imidazole antifungal agent with broad-spectrum activity. However, LCZ encounters challenges such as low aqueous solubility, skin retention, and penetration, which reduce its dermal bioavailability and hinder its efficacy in drug delivery. The aim of the present study was to formulate, characterize, and evaluate the in vitro antifungal efficacy of luliconazole-loaded nanostructured lipid carriers (LCZ-NLCs) against a panel of resistant fungal strains.
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