Delivery of anticancer drug using pH-sensitive micelles from triblock copolymer MPEG-b-PBAE-b-PLA

Abstract

To improve the drug release rate in well-controlled manner, a new pH-sensitive triblock amphiphilic copolymer methyl poly(ethylene glycol) ether-b-poly(β-amino esters)-b-poly lactic acid (MPEG-b-PBAE-b-PLA) and its self-assembled micelles were developed for anticancer drug delivery. The average molecular weight and molecular structure of MPEG-b-PBAE-b-PLA were confirmed by gel permeation chromatography (GPC) and ¹H NMR. The formation of self-assembled micelles, the microstructures at different pH values, and the distribution of doxorubicin (DOX) were investigated by dissipative particle dynamics (DPD) simulation combined with experimental techniques. The copolymers formed stable core-shell-type micelles in water. The critical micelle concentration (CMC) values, particle sizes and zeta potentials of the blank micelles increased along with globule-extended conformational transitions when the pH values decreased from 7.4 to 5.0, due to the protonation of amine groups of PBAE. Obvious increases in the particle sizes and the drug loading content of micelles were observed with increasing DOX. The in vitro release behavior of DOX from the micelles was pH-dependent. The DOX release rate was improved obviously as pH decreased from pH7.4 to pH5.0, with over 96% of DOX was released within 48h. The drug release mechanism under different conditions was also analyzed using theoretical formulas. All the results suggest that the pH-sensitive MPEG-b-PBAE-b-PLA micelles might be a prospective candidate as anticancer drug delivery carrier with well-controlled release behavior.

Keywords: Amphiphilic copolymer; Dissipative particle dynamics simulation; Drug delivery; Drug-loaded micelles; pH-Sensitive.