Synthesis and characterization of a novel polydepsipeptide contained tri-block copolymer (mPEG–PLLA–PMMD) as self-assembly micelle delivery system for paclitaxel

Abstract

A series of biodegradable polydepsipeptides based new triblock copolymers, poly (ethylene glycol)-poly(l-lactide)–poly(3(S)-methyl-morpholine-2,5-dione) (mPEG–PLLA–PMMD) have been synthesized and characterized as self-assembly micelle delivery system for paclitaxel (PTX). Compared to the mPEG2000–PLLA2000 diblock copolymers, the triblock copolymers present more benefits such as lower CMC value, positive-shifted zeta potential, better drug loading efficiency and stability. Among the triblock polymers, mPEG2000–PLLA2000–PMMD1400 micelles present low cytotoxicity and promote the anti-cancer activity of PTX on A-549 and HCT-116cells. In addition, mPEG2000–PLLA2000–PMMD1400 micelles prolongs the circulation time of PTX in rat after i.v. injection (5mg/kg) than that of mPEG2000–PLLA2000 micelles and Taxol®. The half life (t1/2β), mean residence time (MRT), AUC0–∞ and clearance (CL) for PTX-loaded mPEG2000–PLLA2000–PMMD1400 micelles are determined to be 1.941h, 2.683h, 5.220μg/mLh (1.8-fold to mPEG2000–PLLA2000 group), 0.967L/hkg−1, respectively. In conclusion, mPEG2000–PLLA2000–PMMD1400 copolymer could be developed as one of the promising vectors to anti-cancer agents for chemotherapeutics.