Kailasam Velmurugan, Hiremath Manthan S, Sudharsan Pandiyan, Nagarjuna Vasagiri, Garg Prashant, Nirmal Jayabalan
Translational Pharmaceutics Research Laboratory (TPRL), Department of Pharmacy, Birla Institute of Technology and Sciences (BITS), Pilani, Hyderabad Campus, Hyderabad, Telangana 500078, India.
Schrödinger India Private Limited, Bengaluru 560098, India.
Int J Pharm. 2025 Feb 10;670:125149. doi: 10.1016/j.ijpharm.2024.125149. Epub 2024 Dec 28.
Amphotericin B eye drops (reconstituted from lyophilized Amphotericin B formulation indicated for intravenous use) is used off-label for fungal keratitis. However, the reconstituted formulation is stable only for a week, even after refrigeration. Moreover, a high dosing frequency makes it an inconvenient treatment practice. The current study aims to develop a stable Amphotericin B-loaded biomimetic polymeric corneal patch (Ampat) using 3D printing. Hydroxypropyl methylcellulose and chitosan were used to formulate Ampat, which was then characterized for its physical and mechanical properties. The stability studies were performed at different conditions, protected from light. Further, the therapeutic efficacy of Ampat was evaluated against Candida albicans-induced fungal keratitis using ex vivo and in vivo efficacy models. Amphotericin B in Ampat was found to be stable at room temperature (25 °C) and refrigerated conditions for at least two months. Computer simulations showed that the hydrolysis was a major degradation mechanism of Amphotericin B and was reduced when loaded in the polymeric corneal patch. The ex vivo and in vivo studies show that Ampat was as efficacious as the marketed Amphotericin B formulation but with a reduced administration frequency (1 vs 12 times per day). The present study demonstrated Ampat as a potential alternative to reconstituted lipid-bound eye drops to treat fungal keratitis.
两性霉素B滴眼液（由用于静脉注射的冻干两性霉素B制剂复溶而成）被用于真菌性角膜炎的非标签治疗。然而，复溶后的制剂即使冷藏也仅能稳定一周。此外，给药频率高使得这种治疗方法不方便。当前研究旨在利用3D打印技术开发一种稳定的负载两性霉素B的仿生聚合物角膜贴片（Ampat）。使用羟丙基甲基纤维素和壳聚糖来制备Ampat，然后对其物理和机械性能进行表征。在不同条件下进行稳定性研究，并避光保存。此外，使用体外和体内疗效模型评估了Ampat对白色念珠菌引起的真菌性角膜炎的治疗效果。发现Ampat中的两性霉素B在室温（25°C）和冷藏条件下至少两个月内稳定。计算机模拟表明，水解是两性霉素B的主要降解机制，当负载于聚合物角膜贴片中时降解减少。体外和体内研究表明，Ampat与市售的两性霉素B制剂疗效相当，但给药频率降低（每天1次对12次）。本研究证明Ampat是复溶的脂质结合滴眼液治疗真菌性角膜炎的潜在替代品。
