Prodrug Micelles Based on Norbornene-Functional Poly(lactide)s Backbone for Redox-Responsive Release of Paclitaxel

摘要: 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.