Self-assembled micelles prepared from amphiphilic copolymers bearing cell outer membrane phosphorylcholine zwitterions for a potential anti-phagocytic clearance carrier

Abstract

Self-assembled polymeric micelles are widely applied in drug delivery systems to improve the performance of existing therapeutic agents. The aim of this study is to synthesize a series of amphiphilic copolymers of poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) modified poly(ε-caprolactone) P(MPC-co-PCL) and to evaluate the properties of copolymeric micelles and DOX-loaded copolymeric micelles. The results show that the P(MPC-co-PCL) copolymers could self-assemble into micelles of 90 nm to 140 nm. The cytotoxicity of the blank micelles using MTT assay shows no significant cytotoxicity to L929 and HeLa cells even at a high concentration of 0.8 mg mL⁻¹ for 24 h. DOX-loaded P(MPC-co-PCL) micelles could be efficiently internalized into HeLa cells and showed better inhibition of proliferation of the HeLa cell than free DOX. The in vitro phagocytosis results using murine peritoneal macrophages (MPM) show 6-fold reduction compared with PLA nanoparticles as a reference. In addition, P(MPC-co-PCL) copolymeric micelles are quite effective in the encapsulation and controlled release of DOX. These results demonstrate great promise for designing more effective stealth drug carriers that could minimize the clearance of the reticuloendothelial system using simple cell membrane mimetic copolymer micelles.