Formulation and Toxicology of Bone-Targeting Nanoparticles
Bones undergo a renewal process by replenishing calcium mineral through a cellular process known as remodeling. Usually, it happens in a balanced manner, but in many bone diseases, the remodeling process is increased with regional bone metabolism. Bisphosphonate (BP) drugs selectivity and strongly bind to bone mineral and become incorporated at active sites of bone turnover in an increased amount. Accordingly, we have exploited that increased bone metabolism to develop novel bone imaging tracers of metabolism based on BP-conjugated superparamagnetic iron oxide nanoparticles (BP-SPIONs), which localize to remodeling bone surfaces for detection by magnetic resonance imaging (MRI). The current project aims to establish and characterize a stable formulation of the proprietary OsteoMetabolix Pharma BP-SPION, with subsequent toxicity testing in-vitro in cell culture, and in-vivo in rodents (rats), to ascertain minimum effective dose and expected adverse effects of BP-SPIONs as a potential non-ionizing alternative to the technetium radionuclide bone scan.