Preparation and evaluation in vitro and in vivo of fibrinogen microspheres containing adriamycin.

Abstract

Fibrinogen microspheres containing adriamycin were prepared and eveluated as a novel drug delivery system. The shape of the microspheres was invariably spherical. The average diameters were 2.4 and 1.7 μm, and the drug contents in the microspheres were 10.2 and 9.9%, for the microspheres prepared at 110 and 140°C, respectively. Release of the drug from fibrinogen microspheres was slow, and the drug release continued over. 7 d. These results indicated that drug-loaded fibrinogen microspheres could provide a sustained release property in vitro.The antitumor activity of fibrinogen microspheres containing adriamycin was evaluated against Ehrlich ascites carcinoma in mice on the basis of animal survival data. Tumor cell injections were performed on day 0 and microsphere injections on day 1, both intraperitoneally. A prolongation of the life span of tumor-bearing mice following injection of therapeutic microspheres was noted, and the microspheres containing adriamycin were therapeutically more active than adriamycin alone. The high chemotherapeutic efficiency of fibrinogen-adriamycin microspheres was striking at high doses, which would be toxic in the case of the drug alone.These results indicated that fibrinogen microspheres containing adriamycin may be effective in cancer chemotherapy. Microspheres composed of fibrinogen show good biocompatibility and could be useful as a novel drug carrier in injectable delivery systems for anticancer agents.