(348a) Bisphosphonate Modified Gold Nanoparticles to Study Bone Resorption

The bioavailability of a therapeutic agent is integral to its efficacy in treatment regimes. Low bioavailability necessitates increased dosage to achieve desired effects, in turn leading to increased risk and potential for adverse effects. One such example is bisphosphonates, which are a class of drugs used to treat diseases which induce increased bone resorption and bone loss. Low lipophilicity and high negative charge are the properties which most likely contribute to its low bioavailability. Localized delivery is one method of circumventing this effect. In vivo studies have shown localized delivery of bisphosphonates to be effective in inhibiting osteoclastic bone resorption, and thus prevention of femoral head deformity in Legg-Calvé-Perthes disease (LCPD). LCPD is a juvenile form of osteonecrosis of the femoral head, with no known preventive measures. Non-surgical treatment methods are limited. In our research, we have exploited conjugation of bisphosphonates with gold nanoparticles (GNP) and then explored delivery of these nanoparticles into osteoclasts. The optical properties of the GNP allow for in vivo detection of its distribution and retention as it inhibits bone resorption. Results from this work will be presented along with progress in development of an in vitro model to elucidate cellular interactions and response to the functionalized GNP.

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