Abstract
In the current study, poly lactic acid (PLA) modified hollow crosslinked poly(hydroxyethyl methacrylate) (PHEMA) microspheres have been prepared, in order to obtain a stimulus-responsive, biocompatible carrier with sustained drug release properties. The synthetical process consisted of the preparation of poly(methacrylic acid)@poly(hydroxyethyl methacrylate-co-N,N'-methylene bis(acrylamide)) microspheres by a two stage distillation-precipitation polymerization technique using 2,2'-azobisisobutyronitrile as initiator. Following core removal, a PLA coating of the microspheres was formed, after ring opening polymerization of DL-lactide, attributing the initiator's role to the active hydroxyl groups of PHEMA. The anticancer drug daunorubicin (DNR) was selected for the study of loading and release behavior of the coated microspheres. The loading capacity of the PLA modified microspheres was found to be four times higher than that of the parent ones (16% compared to 4%). This coated microspherical carrier exhibited a moderate pH responsive drug release behavior due to the pH dependent water uptake of PHEMA, and PLA hydrolysis. The in vitro cytotoxicity of both the parent and the DNR-loaded or empty modified hollow microspheres has been also examined on MCF-7 breast cancer cells. The results showed that although the empty microspheres were moderately cytotoxic, the DNR-loaded microspheres had more potent anti-tumor effect than the free drug. Therefore, the prepared coated microspheres are interesting drug delivery systems.