Redox-Sensitive Micelles Based on O,N-Hydroxyethyl Chitosan–Octylamine Conjugates for Triggered Intracellular Delivery of Paclitaxel

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• 作者：Meirong Huo ; Yao Liu ; Lei Wang ; Tingjie Yin ; Chen Qin ; Yanyu Xiao ; Lifang Yin ; Jiyong Liu ; Jianping Zhou
• 刊名：Molecular Pharmaceutics
• 出版年：2016
• 出版时间：June 6, 2016
• 年：2016
• 卷：13
• 期：6
• 页码：1750-1762
• 全文大小：708K
• 年卷期：0
• ISSN：1543-8392

文摘

A redox-sensitive micellar system constructed from an O,N-hydroxyethyl chitosan–octylamine (HECS-ss-OA) conjugate with disulfide linkages between the hydrophobic alkyl chains and hydrophilic chitosan backbone was synthesized for triggered intracellular delivery of hydrophobic paclitaxel (PTX). In aqueous environments, conjugates formed micelles with high PTX loading (>30%). Mechanistically, the sensitivity of HECS-ss-OA micelles to reducing environments was investigated using the parameters of in vitro release and particle size. Intracellular release of nile red fluorescence alongside cytotoxicity studies further confirmed the potency of redox-sensitive micelles for intracellular drug delivery compared with redox-insensitive micelles. Additionally, an in vivo study confirmed the efficacy of PTX-loaded micelles in tumor-bearing mice with superior antitumor efficacy and diminished systemic toxicity when compared with the redox-insensitive micelles and a PTX solution. These results demonstrate the potential of redox-sensitive HECS-ss-OA micelles for intracellular trafficking of lipophilic anticancer drugs.