Supramolecular, prodrug-based micelles with enzyme-regulated release behavior for controlled drug delivery
Supramolecular, prodrug-based micelles with enzyme-regulated release behavior for controlled drug delivery
复制标题
具有酶调节释放行为的超分子前药胶束，用于控制药物输送
DOI：
10.1039/c5md00299k
复制
发表时间：
2015-01-01
期刊：
影响因子：
--
通讯作者：
Dong, Chunyan
中科院分区：
文献类型：
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作者：
Li, Yongyong;Chen, Yuqin;Dong, Chunyan
由α-环糊精（α-CD）和聚（ε-己内酯）（PCL）均聚物的主客体相互作用设计的超分子聚合物胶束（SMPM）最近被报道为稳健的药物递送系统。与传统的胶束相比，超分子化学的引入提供了制备方便和性质可控的显著优势。本工作旨在设计和开发由抗癌药物喜树碱携带的PCL（CPT-PCL）和α-CD组装的新型SMPM。开发的前药策略不仅可以引入空间效应以促进超分子纳米组装，而且可以提供防止过早释放以及通过酶调节药物释放的能力。CPT药物和PCL聚合物通过在脂肪酶存在下可水解的酯键连接而化学键合。所得SMPM是球形的，具有约220 nm的流体动力学尺寸和取决于所用PCL的分子量的固定药物比率。进一步评价了载CPT的SMPM的酶促释药行为和细胞毒性，结果表明该胶束在药物控释方面具有良好的应用前景。
Supramolecular polymer micelles (SMPMs) engineered by the host-guest interaction of alpha-cyclodextrin (alpha-CD) and poly(epsilon-capralactone) (PCL) homopolymer have been recently reported as robust drug delivery systems. The incorporation of supramolecular chemistry affords significantly obvious advantages of convenience in fabrication and controllability in properties, in contrast to conventional micelles. This work aims to design and develop novel SMPMs assembled by the anticancer drug camptothecin carrying PCL (CPT-PCL) and alpha-CD. The prodrug strategy developed not only can introduce the steric effect to facilitate the supramolecular nano-assembly but also can provide the capability to prevent the premature release as well as to regulate the drug release by enzymes. The CPT drug and PCL polymer were chemically bonded through an ester bond linkage hydrolyzable in the presence of lipase. The resultant SMPMs were spherical with a hydrodynamic size of around 220 nm and a fixed drug ratio dependent on the molecular weight of PCL employed. The enzyme-induced drug release behavior and cytotoxicity of CPT-carrying SMPMs were further evaluated, and the results revealed the promising application of these micelles for controlled drug delivery.