A Smart pH-Sensitive Delivery System for Enhanced Anticancer Efficacy via Paclitaxel Endosomal Escape

Frontiers in Pharmacology

Yihua Yang¹  Zhe Wang²  Jinsong Ding³  Wenhu Zhou³  Ying Peng³ 

[1] Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmaceutical Sciences, Xuzhou Medical University, Xuzhou, China;Xiangya International Academy of Translational Medicine, Central South University, Changsha, China;Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China;

关键词: pH-sensitive;    micelles;    cancer;    paclitaxel;    endosomal escape;   

DOI  :  10.3389/fphar.2019.00010

来源: DOAJ

【 摘 要 】

Micelles are highly attractive nano-drug delivery systems for targeted cancer therapy. While they have been demonstrated to significantly alleviate the side-effects of their cargo drugs, the therapy outcomes are usually suboptimal partially due to ineffective drug release and endosome entrapment. Stimulus-responsive nanoparticles have allowed controlled drug release in a smart fashion, and we want to use this concept to design novel micelles. Herein, we reported pH-sensitive paclitaxel (PTX)-loaded poly (ethylene glycol)-phenylhydrazone-dilaurate (PEG-BHyd-dC12) micelles (PEG-BHyd-dC12/PTX). The micelles were spherical, with an average particle size of ∼135 nm and a uniform size distribution. The pH-responsive properties of the micelles were certified by both colloidal stability and drug release profile, where the particle size was strikingly increased accompanied by faster drug release as pH decreased from 7.4 to 5.5. As a result, the micelles exhibited much stronger cytotoxicity than the pH-insensitive counterpart micelles against various types of cancer cells due to the hydrolysis of the building block polymers and subsequent rapid PTX release. Overall, these results demonstrate that the PEG-BHyd-dC12 micelle is a promising drug delivery system for cancer therapy.

【 授权许可】

Unknown