Triblock poly(lactic acid)-b-poly(ethylene glycol)-b-poly(lactic acid)/paclitaxel conjugates:: Synthesis, micellization, and cytotoxicity

A triblock poly(lactic acid)-b-poly(ethylene glycol)-b-poly(lactic acid) (PLA-PEG-PLA)/paclitaxel (PTX) conjugate was synthesized by the reaction of carboxyl-terminated copolymer PLA-PEG-PLA with PTX in the presence of dicyclohexylcarbodiimide and dimethylaminopyridine. Carboxyl-terminated copolymer PLA-PEG-PLA was prepared by the reaction of the hydroxyl end groups in copolymer PLA-PEG-PLA with succinic anhydride. Its structure was confirmed by NMR and gel permeation chromatography. The PLA-PEG-PLA/PTX conjugates could self-assemble into micelles in aqueous solutions with a low critical micelle concentration. Dynamic light scattering and environmental scanning electron microscopy analyses of the PLA-PEG-PLA/PTX micelles revealed their spherical structure and size of 220 nm. The antitumor activity of the conjugate against woman Hela cancer cells, evaluated by the 3-(4,5-dimethylthiazol2-yl)-2,5-diphenyl tetrazolium bromide method, showed that the conjugates had an antitumor activity similar to that of pure PTX. The obtained PLA-PEG-PLA/PTX conjugates are expected to be used in clinical practice. (c) 2007 Wiley Periodicals, Inc.