文章基本信息

标题：Nanomicelle formulation for topical delivery of cyclosporine A into the cornea: in vitro mechanism and in vivo permeation evaluation
本地全文：下载
作者：Chuanlong Guo ; Yan Zhang ; Zhao Yang 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2015
卷号：5
期号：1
DOI：10.1038/srep12968
语种：English
出版社：Springer Nature
摘要：A stable topical ophthalmic cyclosporine A (CsA) formulation with good tolerance and high efficacy is still a desire in pharmaceutics and clinics. This article describes the preparation of CsA containing nanomicelles using a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol (PVCL-PVA-PEG) graft copolymer. Both the polymer itself and the CsA nanomicelles were evaluated for cytotoxicity and ocular irritation. The in vitro uptake and intracellular fate of nanomicelles were characterized. In vivo cornea permeation test performed with 0.5 mg/mL CsA containing nanomicelles, and compared with a commercially available CsA (10 mg/mL) oil-based ophthalmic solution. The CsA nanomicelle ophthalmic solution was simple to prepare and remained storage stable. PVCL-PVA-PEG had no cytotoxicity as its monomer solution, and as its micelle solution (IC₅₀(48 h) = 14.02 mg/mL). CsA nanomicelles also had excellent ocular tolerance in rabbits. The use of nanomicelles significantly improved in vitro cellular uptake, apparently by an energy dependent intracellular endocytosis pathway that involved early endosomes, late endosomes, lysosomes, and ER. In vivo permeation showed that 0.5 mg/mL CsA nanomicelles delivered high levels of CsA into the cornea, when compared to the oil-based 10 mg/mL CsA ophthalmic solution. These findings indicated PVCL-PVA-PEG nanomicelles could be a promising topical delivery system for ocular administration of CsA.