Abstract No. 462 Effectiveness and safety transarterial embolization with bleomycin-loaded PLA/PLGA (polylactic acid)(poly[lactic-co-glycolic acid]) microspheres for treatment of vascular malformation using a porcine spleen model

To prospectively study the effectiveness and safety of Bleomycin-loaded PLA/PLGA microparticles in the porcine spleen model. Bleomycin-loaded PLA/PLGA microspheres were manufactured using the double emulsion solvent evaporation method. The porcine spleen was chosen as a vascular malformation model and eleven large Yorkshire pigs were assigned to either the embolization group (n-7) or control group (n-4). Selective angiography was performed in all animals and Bleomycin-loaded PLA/PLGA microspheres (800 –1000 micron in diameter) were administered into the splenic artery in the embolization group. 0.5mg/kg of bleomycin was used per procedure. After 30 days, porcine spleens were acquired to evaluate for the volumes of organ, presence or absence of microspheres, intraluminal reaction to bleomycin, vessel wall changes and extent of sclerosis. Manufactured Bleomycin-loaded PLA/PLGA microsphere formulations showed sustained long-term in-vitro release performance. Transcatheter arterial embolization was technically successful in all animals, without associated complications. Toxicity monitoring showed no hematologic, pulmonary, hepatic or renal toxicities. Bleomycin-loaded PLA/PLGA microspheres induced significant shrinkage in volume of spleens. The mean spleen volume after embolization was significantly (P<0.001) reduced compared with the mean volume for the group control. Pathology showed apoptosis/vasculitis of endothelial cells and disconfiguration of the spleen without systemic side effect in the experimental group. Embolization of the spleen with Bleomycin-loaded PLA/PLGA microspheres with slow release properties can induce strong sclerosis of the spleen locally and promote apoptosis and vasculitis of splenic endothelial cells without systemic side effects. This study shows that transcatheter embolization with Bleomycin-loaded PLA/PLGA microspheres has the potential to be an alternative treatment for vascular malformations in humans.