Calcium phosphate with high specific surface area synthesized by a reverse micro-emulsion method
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Calcium phosphate with high specific surface area synthesized by a reverse micro-emulsion method Tomoaki Sugiyama, Shusuke Akiyama and Toshiyuki Ikoma Department of Metallurgy & Ceramics Science, Tokyo Institute of Technology, Ookayama 2-12-1, Meguro-ku, Tokyo, Japan ABSTRACT A reverse micro-emulsion method has been investigated to control crystal morphology in a nanometer region and to increase specific surface area for calcium phosphate. The nanocrystals with the control of its morphology is a candidate of drug delivery carriers. This study investigated the effects of mixing volume ratios of two surfactants, tween80 (T) and aliquate 336 (A) in kerosene as an oil phase, and pH values in the nano-region on crystalline phases and specific surface area of calcium phosphate synthesized by the reverse micro-emulsion method. A di-ammonium hydrogen phosphate solution including phosphoric acid at pH of 6.3 and a calcium nitrate solution at pH of 5.7 were adjusted, and both the solutions were separately added into the kerosene with the surfactants. Both the emulsions were then mixed at the same volume and the Ca/P ratio of 1.0, and stirred at room temperature for 24 hours. The crystalline phases were dependent on the T amounts; pure DCPD with the specific surface area of 6.7 to 12 m2/g was obtained at the T/A ratio of 4, the mixture of DCPD and DCPA with that of 48 to 162 m2/g was at the ratios of 5 to 8, and a low crystalline HAp with 163 m2/g was at the ratio of 9. These specific surface areas of DCPD (T/A=4) and HAp (T/A=9) were apparently higher than those prepared with a wet method, 7.8 times and 1.8 times respectively. DCPA with 43 m2/g was successfully produced to decrease the pH of phosphate solution at T/A of 9. The change of crystalline phases would be explained as follows; the increase of T amount decreased the micro-emulsion sizes to reduce bulk water to be DCPA, and increased the pH to precipitate HAp nanocrystals. INTRODUCTION Recently, surgical dental treatments for patients who have cancer or osteoporosis and receive intravenous or oral bisphosphonates (BPs) are associated with osteonecrosis of the jaw (Bisphosphonate-Related OsteoNecrosis of the Jaw, BRONJ)1. An administration method of BPs requires carrier material of Bps that administrate to diseased site of osteoporosis by low invasive method and act to osteoclast cells. At this, Drug delivery system (DDS) has become important tools for the specific delivery of a large number of drug molecules. Especially, intelligent DDS has been developed to deliver a drug effectively at targeting sites and to release one when it is required. Intelligent DDS has ability to sense change of external environment or to detect the signal and release appropriate amounts of drugs2. Bps inhibit act of osteoclast cells and improve of osteogenesis on bone remodeling. Bisphosphonates have the ability to selectively adhere and be retained within bone before endocytosis within osteoclasts during osteoclast-mediated bone mineral dissolution and matrix digestion. Cellular apoptosis i
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