Functionalized Calcium Phosphate-based Nanoparticles for the Treatment of Osteoporosis

Abstract

In an effort to decrease the number of problems associated with osteoporosis, the long-term goal of the present study is to design calcium phosphate-based nanoparticles that specifically attach to areas of low bone density and once attached, allow for the targeted release of bioactive agents that can quickly increase bone formation. Efforts are focused on nanoparticles of calcium phosphate-based materials since they are similar in size and chemistry to the major inorganic components of bone. As a first step in this research, the objective of the present study was to synthesize nanoparticles of crystalline hydroxyapatite (or HA) and amorphous calcium phosphate. Crystalline HA is stable under physiological fluids and, thus, will release embedded bioactive agents slowly. Alternatively, amorphous calcium phosphate is highly biodegradable and will, thus, release embedded bioactive agents quickly. A further objective of the present study was to functionalize such inorganic biodegradable materials with amino groups which would allow for the subsequent attachment of entities to direct such nanoparticles to osteoporotic bone and increased bone formation once attached. One promising approach to direct the nanoparticles to osteoporotic bone is to attach antibodies to pentosidine on the nanoparticles since pentosidine is present in higher amounts in osteoporotic compared to healthy bone. A promising approach to increase bone growth once nanoparticles attach to osteoporotic bone, is to embed nanoparticles with regions of the bone growth factor: bone morphogenic protein-2 (or BMP-2). Results of this study demonstrated the successful synthesis of both crystalline HA and amorphous calcium phosphate nanoparticles. Furthermore, results showed that these nanoparticles can be functionalized with versatile amino groups. In this manner, this study takes the first steps toward utilizing calcium phosphate based nanoparticles to reverse bone loss associated with osteoporosis.