Department of Pharmaceutical, School of Pharmacy, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing, 210009, China; Evonik Specialty Chemicals(Shanghai) Co., Ltd, 55Chundong Road Shanghai, 201100, China.
Department of Pharmaceutical, School of Pharmacy, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing, 210009, China.
Carbohydr Polym. 2020 Jan 1;227:115356. doi: 10.1016/j.carbpol.2019.115356. Epub 2019 Sep 20.
Chitosan oligosaccharide-valylvaline-stearic acid (CSO-VV-SA) nanomicelles were designed for topical ocular drug delivery, based on peptide transporter-1 (PepT-1) active targeting. Hydrogenated castor oil-40/octoxynol-40 (HCO-40/OC-40) mixed nanomicelles were also prepared according to Cequa, just approved by FDA. Both nanomicelles produced no significant cytotoxicity and difference in human corneal epithelial cells (HCEpiC) and human conjunctival epithelial cells (HConEpiC). The active transport of CSO-VV-SA nanomicelles by PepT-1 was illustrated in the inhibitory test. Ex vivo fluorescence images of frozen sections indicated that the nanomicelles entered the posterior segment mainly through conjunctival route. In vivo precorneal retention study suggested dexamethasone from both nanomicelles could be detected for more than 3 h in rabbit tears. In vivo distribution evaluation of rabbits' eyes showed the delivering efficiency of CSO-VV-SA nanomicelles was not inferior to that of HCO-40/OC-40 mixed nanomicelles. These findings indicated that CSO-VV-SA nanomicelles could become promising candidates for further clinical application.
壳寡糖-缬氨酸-缬氨酸-硬脂酸（CSO-VV-SA）纳米胶束被设计用于眼部局部药物递送，基于肽转运蛋白 1（PepT-1）的主动靶向。氢化蓖麻油-40/辛基酚聚氧乙烯醚-40（HCO-40/OC-40）混合纳米胶束也根据刚被 FDA 批准的 Cequa 进行了制备。两种纳米胶束在人角膜上皮细胞（HCEpiC）和人结膜上皮细胞（HConEpiC）中均未产生显著的细胞毒性和差异。PepT-1 对 CSO-VV-SA 纳米胶束的主动转运在抑制试验中得到了说明。冷冻切片的体外荧光图像表明，纳米胶束主要通过结膜途径进入后段。在兔眼的预角膜滞留研究中，表明两种纳米胶束中的地塞米松在兔泪液中可检测 3 小时以上。兔眼的体内分布评价表明，CSO-VV-SA 纳米胶束的递送效率不亚于 HCO-40/OC-40 混合纳米胶束。这些发现表明，CSO-VV-SA 纳米胶束可能成为进一步临床应用的有前途的候选物。
