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用于克服眼表屏障的L-缬氨酸修饰的纳米胶束药物递送系统的设计

Design of an L-Valine-Modified Nanomicelle-Based Drug Delivery System for Overcoming Ocular Surface Barriers.

作者信息

Wu Huimin, Xu Yuchen, Cai Mengru, You Longtai, Liu Jing, Dong Xiaoxv, Yin Xingbin, Ni Jian, Qu Changhai

机构信息

School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 102488, China.

出版信息

Pharmaceutics. 2022 Jun 16;14(6):1277. doi: 10.3390/pharmaceutics14061277.

DOI:10.3390/pharmaceutics14061277
PMID:35745853
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9230556/
Abstract

The incidence of ocular surface disease (OSD) is increasing, with a trend towards younger ages. However, it is difficult for drugs to reach the deep layers of the cornea due to ocular surface barriers, and bioavailability is less than 5%. In this study, DSPE-PEG2000 was modified with L-valine (L-Val), and an HS15/DSPE-PEG2000-L-Val nanomicelle delivery system containing baicalin (BC) (BC@HS15/DSPE-PEG2000-L-Val) was constructed using thin-film hydration, with a high encapsulation rate, small particle size and no irritation to the ocular surface. Retention experiments on the ocular surface of rabbits and an in vivo corneal permeation test showed that, compared with the control, nanomicelles not only prolonged retention time but also enhanced the ability to deliver drugs to the deep layers of the cornea. The results of a protein inhibition and protein expression assay showed that nanomicelles could increase uptake in human corneal epithelial cells (HCEC) through energy-dependent endocytosis mediated by clathrin, caveolin and the carrier pathway mediated by PepT1 by inhibiting the overexpression of claudin-1 and ZO-1 and suppressing the expression of PepT1-induced by drug stimulation. These results indicate that BC@HS15/DSPE-PEG2000-L-Val is suitable for drug delivery to the deep layers of the ocular surface, providing a potential approach for the development of ocular drug delivery systems.

摘要

眼表疾病（OSD）的发病率正在上升，且有年轻化趋势。然而，由于眼表屏障，药物难以到达角膜深层，生物利用度低于5%。在本研究中，用L-缬氨酸（L-Val）修饰二硬脂酰磷脂酰乙醇胺-聚乙二醇2000（DSPE-PEG2000），采用薄膜水化法构建了含黄芩苷（BC）的HS15/DSPE-PEG2000-L-Val纳米胶束递送系统（BC@HS15/DSPE-PEG2000-L-Val），其包封率高、粒径小且对眼表无刺激。家兔眼表滞留实验和体内角膜渗透试验表明，与对照组相比，纳米胶束不仅延长了滞留时间，还增强了将药物递送至角膜深层的能力。蛋白质抑制和蛋白质表达测定结果表明，纳米胶束可通过抑制claudin-1和ZO-1的过表达以及抑制药物刺激诱导的PepT1表达，通过网格蛋白、小窝蛋白介导的能量依赖性内吞作用和PepT1介导的载体途径增加人角膜上皮细胞（HCEC）的摄取。这些结果表明，BC@HS15/DSPE-PEG2000-L-Val适用于向眼表深层递送药物，为眼用药物递送系统的开发提供了一种潜在方法。

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