Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin 300384, China.
Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
ACS Infect Dis. 2024 Aug 9;10(8):2950-2960. doi: 10.1021/acsinfecdis.4c00288. Epub 2024 Jul 11.
Fungal keratitis (FK) is a leading cause of preventable blindness and eye loss. The poor antifungal activity, increased drug resistance, limited corneal permeability, and unsatisfactory biosafety of conventional antifungal eye drops are among the majority of the challenges that need to be addressed for currently available antifungal drugs. Herein, this study proposes an effective strategy that employs chitosan-poly(ethylene glycol)-LK peptide conjugate (CPL) in the treatment of FK. Nanoassembly CPL can permeate the lipophilic corneal epithelium in the transcellular route, and its hydrophilicity surface is a feature to drive its permeability through hydrophilic stroma. When encountering fungal cell membrane, CPL dissembles and exposes the antimicrobial peptide (LK) to destroy fungal cell membranes, the minimum inhibitory concentration values of CPL against () are always not to exceed 8 μg peptide/mL before and after drug resistance induction. In a rat model of keratitis, CPL demonstrates superior therapeutic efficacy than commercially available natamycin ophthalmic suspension. This study provides more theoretical and experimental supports for the application of CPL in the treatment of FK.
真菌性角膜炎（FK）是可预防失明和眼盲的主要原因。对于目前可用的抗真菌药物来说，大多数挑战包括抗真菌活性差、耐药性增加、药物有限的角膜通透性和不理想的生物安全性。在此，本研究提出了一种有效的策略，在 FK 的治疗中使用壳聚糖-聚乙二醇-LK 肽缀合物（CPL）。纳米组装 CPL 可以通过细胞外途径穿透亲脂性角膜上皮，其亲水性表面是驱动其通过亲水性基质渗透性的特征。当遇到真菌细胞膜时，CPL 解组装并暴露出抗菌肽（LK）以破坏真菌细胞膜，CPL 对（）的最小抑菌浓度值在耐药诱导前后始终不超过 8μg 肽/mL。在大鼠 角膜炎模型中，CPL 比市售那他霉素眼用混悬液具有更好的治疗效果。本研究为 CPL 在 FK 治疗中的应用提供了更多的理论和实验支持。
