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

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 mPEG ₂₀₀₀-PLLA ₂₀₀₀ 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, mPEG ₂₀₀₀-PLLA ₂₀₀₀-PMMD ₁₄₀₀ micelles present low cytotoxicity and promote the anti-cancer activity of PTX on A-549 and HCT-116 cells. In addition, mPEG ₂₀₀₀-PLLA ₂₀₀₀-PMMD ₁₄₀₀ micelles prolongs the circulation time of PTX in rat after i.v. injection (5 mg/kg) than that of mPEG ₂₀₀₀-PLLA ₂₀₀₀ micelles and Taxol ^®. The half life (t _1/2β), mean residence time (MRT), AUC _0-∞ and clearance (CL) for PTX-loaded mPEG ₂₀₀₀-PLLA ₂₀₀₀-PMMD ₁₄₀₀ micelles are determined to be 1.941 h, 2.683 h, 5.220 μg/mL h (1.8-fold to mPEG ₂₀₀₀- PLLA ₂₀₀₀ group), 0.967 L/h kg ^-1, respectively. In conclusion, mPEG ₂₀₀₀-PLLA ₂₀₀₀-PMMD ₁₄₀₀ copolymer could be developed as one of the promising vectors to anti-cancer agents for chemotherapeutics.