© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.advhealthmat.de www.MaterialsViews.com wileyonlinelibrary.com 678 COMMUNICATION Joshua Chou,* Tomoko Ito, Makoto Otsuka, Besim Ben-Nissan, and Bruce Milthorpe DOI: 10.1002/adhm.201200342 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. Like many pharmaceu- tical drugs, the prescribed methodology for delivering simvas- tatin is by injection [1,2] and oral intake. [3] This can sometimes result in low dosage of the drug being delivered and in most cases, insufficient amounts to exhibit any significant thera- peutic effects. [4] In the case of simvastatin, studies have shown that high concentrations of the drug can result in adverse side effects including liver failure, kidney disease, and rhabdomy- olysis. [5] However, the most common side effects of statins are skeletal muscle complaints, including clinically important myositis and rhabdomyolysis. [6] Rhabdomyolysis is a clinical syndrome in which skeletal muscle damage and necrosis leads to the release of intracellular contents of muscle. The risk of rhabdomyolysis and other adverse effects of statin use can be exacerbated by several factors, including compromised hepatic and renal function, hypothyroidism, diabetes, and concomitant medications. [6] This creates additional challenges in the devel- opment of a suitable carrier, as the potential system must be one that possesses controlled release of the drug to reduce or inhibit the rise of any side effects. The design should allow the system to function to induce and promote key processes in regeneration. To date, the most appropriate concentration of simvastatin to induce bone formation is yet to be determined but studies conducted by other groups have looked at effects at various loadings: 2.2 mg, [7] 0.5 mg; [8,9] 0.1, 0.5, 1.0, 1.5, and 2.2 mg. [10] Furthermore, the development of various carriers for the delivery of simvastatin has also been investigated: meth- ylcellulose gel, [7,9] collagen bovine matrix, [8] gelatin sponge, [9,10] polylactic acid/polyglycolic acid copolymer, [11] and calcium sul- phate. [12,13] However, with potential serious side effects associ- ated with its use, the development of a suitable controlled drug release system is evermore crucial. A biomimicry approach to regenerative medicine is a newly emerging field of research. It will enable the production of better, more effective designs for scaffolds and templates that can be used to store pharmaceutical drugs and deliver them in therapeutic amounts. Fossilized coral exoskeleton (calcium car- bonate; CaCO 3 ) possesses unique architectural structures with interconnected and uniform pore distribution which can poten- tially assist in more predictable drug loading. Furthermore, these exoskeleton structures can be hydrothermally converted into biocompatible calcium phosphate derivatives [14] thereby providing a more predictable dissolution profile depending on the intended application. As part of the degradation of the mate- rial, the breakdown of calcium and phosphate ions can provide the additional supplement for fostering bone formation. With these factors in mind, the purpose of the present work was to prepare and evaluate implanted controlled release drug delivery system of simvastatin using hydrothermally converted beta- tricalcium phosphate ( β-TCP) to treat osteoporotic mice. The conversion to β-TCP was confirmed by powder x-ray dif- fraction analysis ( Figure 1a) with matching peaks compared with JCPDS database. Scanning electron microscopy images show a uniform spherical coating around the β-TCP macro- sphere and this process can be easily reproduced (Figure 1d). To control the release of simvastatin, an outer apatite layer was coated on the material (Figure 1c) to slow the release of the drug ( Figure 2a). For the first 96 h there was no significant change in the release pattern between the coated and uncoated samples. A reduction in the release of simvastatin was only observed for the apatite coated samples after 96 h. The similarity with the initial release is likely due to the release of the drug from the micropores being filled with the buffer solution. It is anticipated that only after the initial release of simvastatin do we begin to observe the slower release of the drug from the delivery system as observed at 120 and 144 h. A longer duration release study is needed to study the long term release profile and to determine Simvastatin-Loaded β-TCP Drug Delivery System Induces Bone Formation and Prevents Rhabdomyolysis in OVX Mice Dr. J. Chou University of Technology Sydney School of Medical and Molecular Sciences Ultimo, Sydney, NSW, 2007, Australia E-mail: Joshua.chou@uts.edu.au Dr. T. Ito Research Institute of Pharmaceutical Science Faculty of Pharmacy Musashino University 1–1-20, Shinmachi, Nishi-Tokyo 202–8585 Japan Prof. M. Otsuka Research Institute of Pharmaceutical Science Faculty of Pharmacy Musashino University 1–1-20, Shinmachi, Nishi-Tokyo 202–8585 Japan Prof. B. Ben-Nissan University of Technology Sydney School of Chemistry and Forensic Sciences Ultimo, Sydney, NSW, 2007, Australia Prof. B. Milthorpe University of Technology Sydney Faculty of Science (CB04.04.48H) Ultimo, Sydney, NSW, 2007, Australia Adv. Healthcare Mater. 2013, 2, 678–681