SYNERGISM OF CALCIUM-ETHANEHYDROXYBISPHOSPHONATE (CAEHBP) AND FEC3 - CONTROLLED-RELEASE POLYMERS FOR PREVENTING CALCIFICATION OF BIOPROSTHETIC AORTIC-WALL

Controlled release delivery implants based on ethylene-vinyl acetate ( EVA) copolymer were studied for prevention of calcification of aortic wall in an intracirculatory rat allograft model. The calcium salt of e thanehydroxybisphosphonate (CaEHBP) and ferric chloride (FeCl3) were u sed as anti-calcification drugs either in combination or separately in solvent-cast EVA films. These matrices were characterized in vitro fo r their drug release at 37 degrees C at pH 7.4 (0.05 M HEPES buffer). Inulin was included in the single drug loaded systems as an inert fill er to obtain comparable loadings. The films released the drugs in vitr o continuously over 60 days without any rapid burst phase. For rat all ograft studies controlled release matrices or non-drug EVA films were sutured periadventitially to the aortic wall allografts to study the a nticalcification efficacy for 30 days, The calcium and phosphorous lev els of the explanted allografts were quantified. Controlled release fi lms releasing both the drugs (CaEHBP and FeCl3) together synergistical ly inhibited calcification of the aortic walls. CaEHBP alone releasing from EVA polymer was partially effective, and EVA films releasing onl y FeCl3 did not inhibit calcification at all, Overall, no adverse effe cts on somatic growth or recipient bone morphology were noted followin g controlled release drug administration.