Controlled delivery of dexamethasone to the intestine from poly(vinyl alcohol)–poly(acrylic acid) microspheres containing drug-cyclodextrin complexes: influence of method of preparation of inclusion complex

Abstract

pH-sensitive interpenetrating polymeric network hydrogel microspheres comprised of poly(vinyl alcohol) and poly(acrylic acid) were synthesized for delivery of dexamethasone (DX) to the intestine. DX is highly active in the treatment of virtually every type of B-cell malignancy; however significant side-effects are invariably associated with it thereby warranting a delivery system that can deliver DX at a controlled rate at the therapeutic level at a specific site. To regulate the release rate of DX, a preformed solid inclusion complex of DX with β-cyclodextrin was added into the hydrogel. In order to find out the influence of the method of preparation of the inclusion complex on the drug delivery process, inclusion complexes were prepared by co-precipitation and freeze-drying methods. Microspheres containing free drug, the physical mixture and the inclusion complexes were synthesized. The microspheres exhibited negligible drug release in the simulated gastric fluid but significant release in the intestinal fluid. The cytotoxicity assay ensured that the microspheres were biocompatible. Thus the synthesized microspheres could be effectively employed for the oral delivery of dexamethasone and their pH sensitivity could be exploited for the intestinal delivery. The microspheres containing the freeze-dried inclusion complexes were found to be the best of the lot for achieving a controlled release of DX. Therefore, it can be proposed that the adverse side-effects of DX could be minimized by using these microspheres as delivery vehicles.