刺激响应性眼用庆大霉素传递壳聚糖纳米粒子水凝胶：配方优化、眼部安全性和抗菌评估。

Stimulus Responsive Ocular Gentamycin-Ferrying Chitosan Nanoparticles Hydrogel: Formulation Optimization, Ocular Safety and Antibacterial Assessment.

机构信息

Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka, Al-Jouf, Kingdom of Saudi Arabia.

Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia.

出版信息

Int J Nanomedicine. 2020 Jun 30;15:4717-4737. doi: 10.2147/IJN.S254763. eCollection 2020.

PURPOSE

The present study was designed to study the gentamycin (GTM)-loaded stimulus-responsive chitosan nanoparticles to treat bacterial conjunctivitis.

METHODS

GTM-loaded chitosan nanoparticles (GTM-CHNPs) were prepared by ionotropic gelation method and further optimized by 3-factor and 3-level Box-Behnken design. Chitosan (A), sodium tripolyphosphate (B), and stirring speed (C) were selected as independent variables. Their effects were observed on particle size (PS as Y1), entrapment efficiency (EE as Y2), and loading capacity (LC as Y3).

RESULTS

The optimized formulation showed the particle size, entrapment efficiency, and loading capacity of 135.2±3.24 nm, 60.18±1.65%, and 34.19±1.17%, respectively. The optimized gentamycin-loaded chitosan nanoparticle (GTM-CHNPopt) was further converted to the stimulus-responsive sol-gel system (using pH-sensitive carbopol 974P). GTM-CHNPopt sol-gel (NSG5) exhibited good gelling strength and sustained release (58.99±1.28% in 12h). The corneal hydration and histopathology of excised goat cornea revealed safe to the cornea. It also exhibited significant (p<0.05) higher ZOI than the marketed eye drop.

CONCLUSION

The finding suggests that GTM-CHNP-based sol-gel is suitable for ocular delivery to enhance the corneal contact time and improved patient compliance.

目的

本研究旨在研究庆大霉素（GTM）负载的刺激响应壳聚糖纳米粒子治疗细菌性结膜炎。

方法

采用离子凝胶法制备 GTM 负载的壳聚糖纳米粒子（GTM-CHNPs），并进一步通过 3 因素 3 水平 Box-Behnken 设计进行优化。壳聚糖（A）、三聚磷酸钠（B）和搅拌速度（C）被选为独立变量。观察它们对粒径（Y1）、包封效率（Y2）和载药量（Y3）的影响。

结果

优化的配方显示粒径、包封效率和载药量分别为 135.2±3.24nm、60.18±1.65%和 34.19±1.17%。优化的庆大霉素负载壳聚糖纳米粒子（GTM-CHNPopt）进一步转化为刺激响应的溶胶-凝胶系统（使用 pH 敏感的卡波姆 974P）。GTM-CHNPopt 溶胶-凝胶（NSG5）表现出良好的胶凝强度和持续释放（12h 内释放 58.99±1.28%）。切除山羊角膜的角膜水化和组织病理学显示对角膜安全。它也表现出比市售滴眼液更高的（p<0.05）更大的 ZOI。