Department of Pharmaceutics, Faculty of Pharmacy and Drug Manufacturing, Misr University for Science and Technology, 12566, 6th of October, Giza, Egypt.
Department of Microbiology and Immunology, Faculty of Pharmacy, October University for Modern Sciences and Arts, 12451, 6th of October, Giza, Egypt.
Drug Deliv Transl Res. 2024 Sep;14(9):2520-2538. doi: 10.1007/s13346-024-01527-8. Epub 2024 Feb 16.
Candida species is one of the pathogenic fungi of the eye responsible for keratitis that frequently causes vision impairment and blindness. Effective treatment requires long-term use of antifungal drugs, which is opposed by the defensive mechanisms of the eye and inadequate corneal penetration. The objective of this study was to develop a carrier for prolonged ocular application of fluconazole (FLZ) to treat keratitis. FLZ was encapsulated into chitosan fibrous matrices (F1-F4) using different chitosan concentrations (0.02, 0.1, 0.5, and 1%w/v, respectively) by freeze-drying as a single-step technique. Studying the morphology and surface properties of the inserts revealed a porous matrix with fibrous features with a large surface area. Thermal stability and chemical compatibility were confirmed by DSC/TGA/DTA and FT-IR, respectively. Loading capacity (LC) and entrapment efficiency (EE) were determined. According to the in vitro release study, F4 (0.11 mg mg LC and 87.53% EE) was selected as the optimum insert because it had the most sustained release, with 15.85% burst release followed by 75.62% release within 12 h. Ex vivo corneal permeation study revealed a 1.2-fold increase in FLZ permeation from F4 compared to FLZ aqueous solution. Also, in the in vivo pharmacokinetic study in rabbits, F4 increased the AUC of FLZ by 9.3-fold and its concentration in aqueous humor was maintained above the MIC through the experimentation time. Studies on cytotoxicity (MTT assay) provide evidence for the safety and biocompatibility of F4. Therefore, the freeze-dried FLZ-loaded chitosan fibrous insert could be a promising candidate for treating ocular keratitis.
念珠菌属是引起角膜炎的致病性真菌之一，常导致视力损害和失明。有效的治疗需要长期使用抗真菌药物，但这与眼睛的防御机制和角膜穿透不足相矛盾。本研究旨在开发一种用于延长氟康唑（FLZ）眼部应用的载体，以治疗角膜炎。FLZ 被包封到壳聚糖纤维基质（F1-F4）中，使用不同的壳聚糖浓度（分别为 0.02、0.1、0.5 和 1%w/v），通过冷冻干燥作为单一技术。研究插塞的形态和表面特性表明，具有大表面积的多孔基质具有纤维特征。DSC/TGA/DTA 和 FT-IR 分别证实了热稳定性和化学相容性。载药量（LC）和包封效率（EE）被确定。根据体外释放研究，选择 F4（LC 为 0.11mg mg 和 EE 为 87.53%）作为最佳插塞，因为它具有最持久的释放，释放 15.85%的突释后，在 12 小时内释放 75.62%。离体角膜渗透研究表明，与 FLZ 水溶液相比，F4 中 FLZ 的渗透增加了 1.2 倍。此外，在兔体内药代动力学研究中，F4 将 FLZ 的 AUC 增加了 9.3 倍，并且在实验期间，其房水中的浓度保持在 MIC 以上。细胞毒性（MTT 测定）研究为 F4 的安全性和生物相容性提供了证据。因此，负载 FLZ 的冷冻干燥壳聚糖纤维插塞可能是治疗眼部角膜炎的有前途的候选物。
