SYNTHESIS AND PROPERTIES OF DIBLOCK COPOLYMERS OF POLY(ETHYLENE GLYCOL) AND POLY(2-METHOXYETHYL ETHYLENE PHOSPHATE) FOR ENHANCED PACLITAXEL SOLUBILITY

Abstract

A series of block copolymers of methoxy poly(ethylene glycol) and poly(2-methoxyethyl ethylene phosphate)(MPEG-b-PMOEEP) were synthesized using methoxy poly(ethylene glycol)(MPEG) as the initiator and tin(II) 2-ethylhexanoate as the catalyst.The polymers were characterized by gel permeation chromatograph(GPC) and nuclear magnetic resonance(NMR).After dissolved in water directly,the block polymers self-assembled into polymeric micelles with PMOEEP as the hydrophobic core and MPEG as the hydrophilic shell.They were used for hydrophobic anticancer drug paclitaxel(PTX) solubilization.It was found that the solubility of PTX in aqueous solutions was greatly enhanced after addition of the polymers,and was significantly affected by polymer composition and concentrations.Increasing weight ratio of PMOEEP block of the polymer resulted in enhanced PTX solubility,and PTX solubility was increased with the increase of polymer concentration that was correlative to the micellization process of the block polymer in aqueous solutions.The polymers were proved to be biodegradable and biocompatible.1H-NMR spectra were used to demonstrate the degradability of PMOEEP by phosphodiesterase(I).MTT assay revealed these block copolymers were nontoxic to breast cancer cells MCF-7 up to a concentration of 10 mg mL-1,while the activity of PTX solubilized by MPEG-b-PMOEEP polymer against MCF-7 cells was comparable to free PTX dissolved in dimethyl sulfone,indicating these polymers are potential materials for enhanced PTX solubility.