Chomchalao Pratthana, Saelim Nuttawut, Lamlertthon Supaporn, Sisopa Premnapa, Tiyaboonchai Waree
Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok 65000, Thailand.
College of Medicine and Public Health, Ubon Ratchathani University, Ubon Ratchathani 34190, Thailand.
Polymers (Basel). 2024 Jan 3;16(1):148. doi: 10.3390/polym16010148.
The purpose of this work was to investigate the feasibility of a novel ophthalmic formulation of amphotericin B-encapsulated silk fibroin nanoparticles incorporated in situ hydrogel (AmB-FNPs ISG) for fungal keratitis (FK) treatment. AmB-FNPs ISG composites were successfully developed and have shown optimized physicochemical properties for ocular drug delivery. Antifungal effects against and in vitro ocular irritation using corneal epithelial cells were performed to evaluate the efficacy and safety of the composite formulations. The combined system of AmB-FNPs-ISG exhibited effective antifungal activity and showed significantly less toxicity to HCE cells than commercial AmB. In vitro and ex vivo mucoadhesive tests demonstrated that the combination of silk fibroin nanoparticles with in situ hydrogels could enhance the adhesion ability of the particles on the ocular surface for more than 6 h, which would increase the ocular retention time of AmB and reduce the frequency of administration during the treatment. In addition, AmB-FNP-PEG ISG showed good physical and chemical stability under storage condition for 90 days. These findings indicate that AmB-FNP-PEG ISG has a great potential and be used in mucoadhesive AmB eye drops for FK treatment.
本研究旨在探讨一种新型的两性霉素B包裹的丝素蛋白纳米粒原位水凝胶（AmB-FNPs ISG）眼科制剂用于治疗真菌性角膜炎（FK）的可行性。成功制备了AmB-FNPs ISG复合材料，并显示出其在眼部药物递送方面具有优化的物理化学性质。通过对角膜上皮细胞进行抗真菌作用及体外眼刺激试验，以评估复合制剂的疗效和安全性。AmB-FNPs-ISG联合系统表现出有效的抗真菌活性，且对人角膜上皮（HCE）细胞的毒性明显低于市售两性霉素B。体外和离体粘膜粘附试验表明，丝素蛋白纳米粒与原位水凝胶的组合可增强颗粒在眼表的粘附能力超过6小时，这将增加两性霉素B在眼部的滞留时间并减少治疗期间的给药频率。此外，AmB-FNP-PEG ISG在90天的储存条件下表现出良好的物理和化学稳定性。这些结果表明，AmB-FNP-PEG ISG具有巨大潜力，可用于制备用于治疗FK的粘膜粘附性两性霉素B滴眼液。
