Smart micelles self-assembled from four-arm star polymers as potential drug carriers for pH-triggered DOX release

Abstract

A series of amphiphilic four-arm star polymers poly(e-caprolactone)-b-poly(2-(diethylamino)ethylmethacrylate) (4AS-PCL-b-PDMAEMA) were developed by a combination of ring opening polymerization (ROP) and continuous activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP). The molecular structures of the copolymers were confirmed with 1H NMR, FT-IR and gel permeation chromatography (GPC). The critical micelle concentration (CMC) values of the star polymers in aqueous solution were extremely low (3.0–4.1 mg/L).In aqueous solution, the copolymers self-assemble into blank and doxorubicin (DOX)-loaded micelles with an average size of 56–150 nm measured by scanning electron microscopy (SEM) and dynamic light scattering (DLS), which consist of outer shell with blocks PDMAEMA and inner core with blocks PCL. The core block PCL was used to contain drug molecules and shell block PDMAEMA could protonize responding to acidic condition. The in vitro release behavior showed that the micelle structure remains basically unchanged, and the drug cumulative release was only 24.5% at pH 7.4, and at pH 5.0, PDMAEMA is protonated and the micelles swell, which accelerates the release rate of DOX and the cumulative release is higher than pH 7.4. Through the semi-empirical model, the mechanism of drug release process was analyzed, and the mechanism of drug release from polymer micelles was further explored. The in vitro cytotoxicity indicated that the 4AS-PCL-b-PDMAEMA materials had low toxicity, but the DOX-loaded micelles had an obvious inhibitory effect on the HepG2 cells. The results indicate the four-arm star polymers 4AS-PCL-b-PDMAEMA may be a potential drug carriers for pH-triggered DOX release.