Albumin microspheres as a drug delivery system for epirubicin: pharmaceutical, pharmacokinetic and biological aspects

Abstract

The aim of the present work was to investigate the effectiveness of epirubicin-loaded microspheres to affect specific organ or tissue sites where tumors are present. Egg albumin microspheres were prepared using a heat denaturation method. The kinetics of in vitro release of the drug complied partially with first order ( r = 0.9894) as well as with diffusion model from a matrix ( r = 0.9982). The pharmacokinetics of epirubicin in serum, heart and lungs after a single i.v. dose of free epirubicin and epirubicin-loaded microspheres in rats could be described by the equation of the two-compartment open model. The pharmacokinetic parameters calculated suggest the possibility to improve the selective entrapment of epirubicin-loaded microspheres by the lungs. The aim of our efficacy studies was to evaluate intratumoral administration of epirubicin-loaded microspheres in mice with Ehrlich ascites carcinoma, as well as experimental metastases in 256 rats with Walker carcinoma. The difference between the mean survival time, respectively the final metastatic incidences of the animals from treated groups compared to controls and to the free-epirubicin group, were statistically significant. These findings suggest the possibility of organ targeting and of reducing unwanted side-effects, especially the cardiotoxicity, of the epirubicin-loaded microspheres in cancer chemotherapy.