(696e) Developing An Injectable Drug Delivery System to Treat Perthes Disease

Perthes disease is an idiopathic condition that affects approximately 1 out of 1200 children, generally between the ages of 4 and 10 years. Although the inciting event is not fully understood, the results include the disturbance of the vascular supply to the proximal femur and tissue necrosis. The collapse of the bone and growth disturbance creates a clinically devastating result. In this study, an injectable, polymer-based drug delivery system has been developed for controlled, localized release of an antiresorptive agent (clodronate) to inhibit collapse of the femoral head that is sequentially followed by an osteogenic biomolecule (BMP-2 or simvastatin) to stimulate bone regeneration. Such a delivery system could be a viable clinical approach. The delivery system consists of carboxymethylcellulose (CMC) and gelatin biopolymers loaded with clodronate and BMP-2/simvastatin, respectively. The microspheres of gelatin are suspended in a viscous solution of CMC for eventual injection into the diseased femoral head. The release profile of clodronate was controlled by modifying the viscosity of the CMC solution and loading of drug, whereas the release profile of osteogenic biomolecule was controlled by adjusting the crosslink density of gelatin microspheres and amount of protein/drug loaded. Preliminary studies demonstrated that different concentrations of clodronate could be released by simple diffusion within up to 12 hours to achieve rapid inhibition of bone resorption. Release of the osteogenic biomolecules can be delayed and subsequently last up to 12 days. This biphasic delivery system has potential for modulating pathophysiological events during complex disease processes.