title: The effectiveness of the controlled release of simvastatin from β-TCP macrosphere in the treatment of OVX mice.
abstract: Simvastatin, a cholesterol treatment drug, has been shown to stimulate bone regeneration. As such, there has been an increase interest in the development of suitable materials and systems for the delivery of simvastatin. Without the appropriate dosage of simvastatin, the therapeutic effects on bone growth will be significantly reduced. Furthermore, similar to many pharmaceutical compounds, at high concentration simvastatin can cause various adverse side-effects. Given the associated side-effects with the usage of simvastatin, the development of suitable controlled drug release system is pertinent. Calcium phosphate in particularly beta-tricalcium phosphate (β-TCP) has been extensively studied and used as a carrier material for drug delivery system. In this study, Foraminifera exoskeletons were used as calcium carbonate precursor materials, which were hydrothermally converted to β-TCP as a carrier material for simvastatin. Natural marine exoskeletons posses interconnected and uniformly porous network capable of improving drug loading and release rate. To prolong the release of simvastatin, an apatite coating was made around the β-TCP sample and in vitro release studies in simulated body fluid (SBF) showed a significant decrease in release rate. Osteoporotic mice were used to examine the compare therapeutic effectiveness of β-TCP, β-TCP with simvastatin, apatite-coated β-TCP with simvastatin and direct injection of simvastatin near the right femur of the mice. Localized and systemic effect were compared with the femur of the non-implanted side (left) and showed that β-TCP with or without simvastatin was able to induce significant bone formation over 6 weeks. Mechanical analysis showed that apatite-coated β-TCP with simvastatin produced significantly stronger bones compared with other experimental groups. This study shows that natural exoskeletons with the appropriate structure can be successfully used as a drug delivery system for simvastatin and can its release can be prolonged with an apatite coating to significantly promote relevant bone formation.
authors.affiliation: The University of Technology Sydney, Advanced Tissue Regeneration and Drug Delivery Group, School of Medical and Molecular Sciences, Ultimo, Sydney, Australia.
authors.forename: Joshua
authors.initials: J
authors.lastname: Chou
authors.affiliation: Musashino University, Research Institute of Pharmaceutical Science, Faculty of Pharmacy, Nishi-Tokyo, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ito
authors.affiliation: Musashino University, Research Institute of Pharmaceutical Science, Faculty of Pharmacy, Nishi-Tokyo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Otsuka
authors.affiliation: The University of Technology Sydney, School of Chemistry and Forensic Sciences, Ultimo, Sydney, NSW, Australia.
authors.forename: Besim
authors.initials: B
authors.lastname: Ben-Nissan
authors.affiliation: The University of Technology Sydney, Dean of Science, Faculty of Science, Ultimo, Sydney, NSW, Australia.
authors.forename: Bruce
authors.initials: B
authors.lastname: Milthorpe
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D002130:Calcium Phosphates / Q000737:chemistry*; D003692:Delayed-Action Preparations; D018483:Diaphyses / Q000187:drug effects / Q000502:physiology; D005260:Female; D005269:Femur / Q000187:drug effects / Q000502:physiology; D020007:Implants, Experimental; D051379:Mice; D010012:Osteogenesis / Q000187:drug effects; D010052:Ovariectomy; D019821:Simvastatin / Q000008:administration & dosage* / Q000494:pharmacology*; D054457:Tissue Scaffolds / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D002130:Calcium Phosphates; D003692:Delayed-Action Preparations; C485817:beta-tricalcium phosphate; D019821:Simvastatin
keywords: OVX; biomimetic; controlled release; coral; drug delivery system; osteoporosis; simvastatin