Preparation and Drug Release Properties of a Novel PLA-PEG-PTX Pro-Drug

Abstract

Lactide (LA) and PEG as raw materials, 2,2-Dimethylol Propionic Acid (DMPA) as initiator, hexamethylene diisocyanate (HDI) as coupling agent, amphiphilic block copolymer PLA-PEG with side carboxyl group was synthesized. A novel PLA-PEG-PTX pro-drug was prepared through the esterification reaction between the side carboxyl group on copolymer and hydroxyl group on paclitaxel. Its structure was characterized with 1H-NMR and FT-IR. The pro-drug micelles were prepared by solvent evaporation method. The particle size of the micelles was determined by nanoparticle tracking analyzer, the micro structure of the micelles was determined by TEM, and the drug release properties were investigated by dialysis experiments. Results showed that the pro-drug micelles are spherical with core-corona structure and major particles size in 55-85nm. The PLA-PEG750-PTX (molar ratio of LA to DMPA as 40 to 1) pro-drug micelles released paclitaxel slowly and steadily without obvious burst release in buffer solution with pH=7.0, and its cumulative release rate reached to 36% in 10 hours. PLA-PEG750-PTX pro-drug micelles have a certain sustained-release effect, which is beneficial to improve the anti-tumor effect of paclitaxel.