Synthesis and Self-Assembly of the pH-Responsive Anionic Copolymers for Enhanced Doxorubicin-Loading Capacity

Polyelectrolyte complex micelles self-assembled from an ionic polymer and oppositely charged small molecules are a promising drug delivery system. In this study, the anionic block copolymers composed of poly(ethylene glycol), poly(ε-caprolactone), and carboxyl modified poly(ε-caprolactone), COOH-PCEC, were designed to encapsulate doxorubicin (DOX) via electrostatic and hydrophobic interactions to form spherical micelles with a particle size of 90-140 nm. The higher payload capacity of these micelles than noncharged micelles of PCL-poly(ethylene glycol)-PCL (PCEC) was achieved, and it was strongly dependent on the composition of the micelles. In vitro drug release studies showed that the release of DOX from the micelles was faster at pH 5.5 than at pH 7.4, which was mainly due to the protonation of carboxyl groups and the solubility of DOX. Studies of intracellular uptake demonstrated that the DOX-loaded micelles could be internalized effectively by HeLa cells. In vitro cytotoxicity revealed that the blank COOH-PCEC micelles had a low cytotoxicity against both L929 and HeLa cells. However, the DOX-loaded micelles inhibited the growth of HeLa cells remarkably, demonstrating their potential for use as an efficient carrier for the delivery of DOX.