Functionalized Calcium Phosphate-based Nanoparticles for the Treatment of Osteoporosis
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Functionalized Calcium Phosphate-based Nanoparticles for the Treatment of Osteoporosis Balasundaram G1, Sato M2, and Webster TJ 1, 2 1
Weldon School of Biomedical Engineering School of Materials Engineering Purdue University, West Lafayette, IN, 47907, USA. 2
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. INTRODUCTION Although osteoporosis has been studied for a number of years, no current effective prevention and treatment methods exist for this disease. It is clear, however, that low bone mass is a strong predictor of future fractures and this risk occurs during the normal course of aging, during unloading of the skeleton (e.g., bed-rest after surgery, lack of exercise), as a consequence of certain diseases (e.g., arthritis, osteoporosis), and as a side effect of various drug therapies (e.g., hormone replacements, steroids). Various countermeasures (e.g., drugs, diet, and physical activity) have been developed and studied for the prevention and treatment of osteoporosis. Similarly, efforts have been made to improve materials and drugs used to treat fractures and promote bone healing. None have
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