Characterization and anticalcification effects of implantable polyurethane matrices containing amorphous dispersion of bisphosphonic acid

Cardiovascular calcification, the formation of calcium phosphate deposits in cardiovascular tissue, is a common-end stage phenomenon affecting a wide variety of cardiovascular disease states and causing the dysfunction of many different types of biomaterial implants. The present investigation describes the formulation, characterization, and the in-vivo efficacy of prolonged controlled-release polyurethane matrices containing the anticalcification agent 1,1-hydroxyethylidene bisphosphonic acid (HEBP). Sustained-release polyurethane (PU) matrices with amorphous dispersion of the drug, in its free acid form, were obtained. Matrices morphology and release kinetics were solvent and concentration dependent. All HEBP matrices (co-implanted subdermally in rats with the calcifiable bioprosthetic heart valve tissue) significantly inhibited tissue calcification (76·3 μg/mg Cal⁺⁺ in comparison to 1·1-10·1 μg/mg Cal⁺⁺, untreated and treated groups, respectively). Systemic side effects were noted only in the rats implanted with the 30 % w w HEBP matrices. It is concluded that PU matrices with amorphous dispersion of HEBP provided effective and sustained anti-calcification properties.