Optimized preparation of daidzein-loaded chitosan microspheres and in vivo evaluation after intramuscular injection in rats

A spherical symmetric design-response surface methodology was applied to optimize the preparation of daidzein-loaded chitosan microspheres by the emulsification/chemical cross-linking technique. The influence of polymer concentration, ratio of drug to polymer, and the stirring speed on the encapsulation efficiency, particle size, particle size distribution, and accumulative drug release percent in microspheres were evaluated. Scan electron microscopy of the optimized microspheres showed spherical particles, loading with drug microcrystal uniformly on the surface of and inside the microspheres. In vivo pharmacokinetic characteristics were evaluated after intramuscular injection of the microspheres in rats. The time-resolved fluoroimmunoassay method was used to determine plasma concentrations of daidzein. The data showed that the release of daidzein in the microspheres in vitro and in vivo almost lasted for 35 days. The bioavailability of daidzein in the microspheres by intramuscular injection increased up to 39% in rats, suggesting that the cross-linked chitosan microspheres are a valuable system for the long-term delivery of isoflavones. (c) 2007 Elsevier B.V. All rights reserved.