Improving Physicochemical Properties and Doxorubicin Cytotoxicity of Novel Polymeric Micelles by Poly(ε-Caprolactone) Segments

This study constructed a series of novel micelles based on star-shaped amphiphilic copolymers (sPEC/CDs), and aimed to confirm the important role poly(epsilon-caprolactone) (PCL) segments played to improve the various properties of micelles. sPEC/CDs, consisting of beta-cyclodextrin (beta-CD) as a core and monomethoxy poly(ethylene glycol) (mPEG) and PCL di-block copolymers as arms, were synthesized by arm-first method. The critical micelle concentrations (CMC) of sPEC/CDs were determined by fluorescence spectrophotometry using pyrene as a probe. 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and flow cytometry were used to detect drug cytotoxicity and cellular uptake of the doxorubicin-loaded micelles. Rhodamine-123 cellular accumulation was examined to evaluate the polymer action to P-glycoprotein. It was revealed that, once PCL segment was inserted between beta-CD and mPEG, the CMC can be significantly decreased, the drug loading capability greatly improved, and the drug resistance of MCF-7/ADR cells effectively reversed. These findings suggest that sPEC/CDs own potential superiority for cancer therapy as drug carriers. (C) 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:2430-2442, 2011