Self-assembly and in vitro drug release behaviors of amphiphilic copolymers based on functionalized aliphatic liquid crystalline polycarbonate with pH/temperature dual response

Abstract

Amphiphilic copolymers Pn (n = 1–3) with mPEG as hydrophilic segment and aliphatic polycarbonate as hydrophobic segment were designed and synthesized successfully, and the results of POM, XRD and DSC showed that only P3 showed liquid crystalline (LC) phase. Due to the carboxyl and cholesteric LC groups in the side chain of the polycarbonate, the micelles prepared in this study were endowed with pH and temperature dual response. The effects of different conditions such as selective solvents, copolymer concentration, pH, temperature, the structure and LC mesophase on the self-assembly behavior and drug loading properties of the copolymer micelles were explored. It was found that the critical water concentration for self-assembly, the particle size and morphology of the micelles could be effectively controlled by changing the above conditions. Moreover, introducing LC properties into the copolymer could effectively decrease the critical water concentration for self-assembly and elevate the drug loading content. The DOX was conjugated to the copolymers by hydrogen bonds, and the copolymer P3 could form regular fusiform micelles after loading with DOX. Moreover, P3-DOX micelles could be endocytosed into cells and the drug release behavior could be triggered by the weak acid condition and elevated temperature. Therefore, the P3-DOX micelles could achieve a pH-triggered rapid drug release under weakly acidic conditions of the tumor cells. This kind of controllable micelles will have a potential application as drug-carriers in drug delivery.