Prodrug Micelles Based on Norbornene-Functional Poly(lactide)s Backbone for Redox-Responsive Release of Paclitaxel
Ji Wang A , Jing Yan A , Huicong Zhou A , Haikang Huang A , Xuefei Zhang A B C and Haoyu Tang A B C
+ Author Affiliations
- Author Affiliations
A College of Chemistry, Xiangtan University, Xiangtan, 411105, Hunan Province, China.
B Key Laboratory of Environmentally Friendly Chemistry and Applications of Ministry of Education, Key Laboratory of Polymeric Materials and Application Technology of Hunan Province, and Universities of Hunan Province, Xiangtan, 411105, China.
C Corresponding authors. Email: zxf7515@163.com; htang@xtu.edu.cn
Australian Journal of Chemistry 69(10) 1140-1148 https://doi.org/10.1071/CH16100
Submitted: 20 February 2016 Accepted: 31 March 2016 Published: 3 May 2016
Abstract
Norbornene-functional poly(lactide)s backbone-based amphiphilic copolymer, P(LA-g-mOEG)-b-P(LA-SS-COOH), was synthesized as the polymeric scaffold and paclitaxel (PTX) was directly conjugated to the carboxyl groups of the amphiphilic copolymer to obtain redox-responsive P(LA-g-mOEG)-b-P(LA-SS-PTX) prodrugs. The dynamic light scattering and transmission electron microscopy analyses showed that P(LA-g-mOEG)-b-P(LA-SS-PTX) self-assembled into prodrug micelles with a diameter of 60–70 nm and a low polydispersity in aqueous solution. Remarkably, in vitro release studies revealed that 80 % of PTX was released in 72 h under a reductive environment, whereas only 23 % of PTX was released in 72 h under non-reductive conditions. In addition, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays showed that P(LA-g-mOEG)-b-P(LA-SS-PTX) prodrug micelles retained high anti-tumour activity while polymer carriers were non-toxic up to a tested concentration of 1.0 mg mL–1. These redox-responsive prodrug micelles have tremendous potential for anti-tumour drug delivery.
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