title: Preparation of calcium phosphate nanocapsules including simvastatin/deoxycholic acid assembly, and their therapeutic effect in osteoporosis model mice.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
authors.affiliation: Research Institute of Pharmaceutical Sciences, Musashino University, Tokyo, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ito
authors.forename: Manami
authors.initials: M
authors.lastname: Takemasa
authors.forename: Kimiko
authors.initials: K
authors.lastname: Makino
authors.forename: Makoto
authors.initials: M
authors.lastname: Otsuka
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use; D001842:Bone and Bones / Q000187:drug effects; D002130:Calcium Phosphates / Q000009:adverse effects / Q000737:chemistry*; D002460:Cell Line; D003840:Deoxycholic Acid / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use; D004195:Disease Models, Animal; D004339:Drug Compounding; D016503:Drug Delivery Systems / Q000009:adverse effects; D005260:Female; D006801:Humans; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use; D051379:Mice; D008815:Mice, Inbred Strains; D008823:Micelles; D053769:Nanocapsules / Q000009:adverse effects / Q000737:chemistry*; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*; D011897:Random Allocation; D019821:Simvastatin / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use; D013499:Surface Properties; D013501:Surface-Active Agents / Q000009:adverse effects / Q000737:chemistry
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D050071:Bone Density Conservation Agents; D002130:Calcium Phosphates; D000960:Hypolipidemic Agents; D008823:Micelles; D053769:Nanocapsules; D013501:Surface-Active Agents; D003840:Deoxycholic Acid; C020243:calcium phosphate; D019821:Simvastatin