Preparation and anticancer activity evaluation of self-assembled paclitaxel conjugated MPEG-PCL micelles on 4T1 cells

Abstract

In this study, we prepared self-assembled micelles with methoxy poly(ethylene glycol)-b-poly(ε-caprolactone) (MPEG-PCL) for paclitaxel (PTX) delivery. MPEG-PCL was synthesized by ring-opening polymerization in which the hydroxyl group was substituted for a carboxyl group by succinic anhydride. PTX was then coupled to carboxylated MPEG-PCL through esterification (MPEG-PCL-PTX). MPEG-PCL-PTX micelles were prepared by a solvent evaporation method. Conjugation of PTX to MPEG-PCL-PTX was confirmed by 1H NMR. MPEG-PCL-PTX micelles self-assembled into micellar nanoparticles at concentrations above 2.5×10−2mg/mL, as evaluated by fluorescence spectrometry. DLS and TEM analyses revealed that the micelles were globular in shape with an average size of 111nm. The drug release studies under three pH conditions demonstrated that PTX release from MPEG-PCL-PTX micelles was entirely dependent upon the hydrolysis of ester bond between PTX and MPEG-PCL copolymer, therefore, no severe initial burst release but pH sensitive profile was observed. In vitro tests with the 4T1 cell line showed that conjugation of PTX to MPEG-PCL led to improved cellular uptake and apoptosis compared to free PTX, supporting the feasibility of using the micelles as drug carriers for cancer therapy.