Preparation of calcium phosphate nanocapsules including simvastatin/deoxycholic acid assembly, and their therapeutic effect in osteoporosis model mice

Abstract

Objectives 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. Methods 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. Key findings 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. Conclusions Such biocompatible CaP nanocapsules including deoxycholate micelles is expected to be a novel strategy to construct an effective device for delivery of hydrophobic drugs. © 2012 The Authors. JPP © 2012. Royal Pharmaceutical Society.