deoxycholic-acid and Osteoporosis--Postmenopausal

Simvastatin has recently been demonstrated to serve as a therapeutic agent for osteoporosis. However, it is hard to dissolve in water and has side effects such as rhabdomyolysis. Solubilization of the drug by deoxycholate was attempted, and the resulting simvastatin/deoxycholate assembly (DeCA/Sim) was coated by calcium phosphate (CaP) to reduce the side effects of simvastatin. The aim of this study was to examine the therapeutic effects of the CaP-coated deoxycholate micelle containing simvastatin in osteoporosis model mice.. Deoxycholate micelle containing simvastatin coated by CaP (CaP-DeCA/Sim) was prepared by immersion of deoxycholate/simvastatin assembly in simulated body fluid (SBF). The therapeutic effect of CaP-DeCA/Sim on osteoporosis model mice was evaluated by X-ray computed tomography, and also its effect on other body conditions.. The CaP coating remarkably reduced cytotoxicity in cultured cells. When CaP-DeCA/Sim was injected into ovariectomized mice, inflammation was suppressed, and led to a whole-body therapeutic effect (body weight, bone mineral content and bone mechanical strength). The deoxycholic acid/simvastatin assembly coated by CaP is thus useful for the treatment of osteoporosis.. Such biocompatible CaP nanocapsules including deoxycholate micelles is expected to be a novel strategy to construct an effective device for delivery of hydrophobic drugs.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Bone and Bones; Bone Density Conservation Agents; Calcium Phosphates; Cell Line; Deoxycholic Acid; Disease Models, Animal; Drug Compounding; Drug Delivery Systems; Female; Humans; Hypolipidemic Agents; Mice; Mice, Inbred Strains; Micelles; Nanocapsules; Osteoporosis, Postmenopausal; Random Allocation; Simvastatin; Surface Properties; Surface-Active Agents