Development of Bisphosphonate-Calcium Phosphate Composites and Drug Release Characteristic
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Development of Bisphosphonate-Calcium Phosphate Composites and Drug Release Characteristic Hidekuni Kameda1, Tomohiko Yoshioka1, Toshiyuki Ikoma1, and Junzo Tanaka1 1 Department of Metallurgy and Ceramics Science, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo, 152-8550 Japan ABSTRACT Bisphosphonate (Bp) was adsorbed on the surface of crystalline calcium phosphates (CP); hydroxyapatite (HAp), octacalcium phosphate (OCP) and Dicalcium phosphate dehydrate (DCPD). The amount of Bp adsorbed was the largest for DCPD per unit surface area, while the amount was the largest for HAp per unit weight. The composites of Bp and amorphous calcium phosphate (ACP) were synthesized by titrating calcium acetate solution into phosphate buffer solution containing Bp. The amount of Bp doped in the composites was 366 μg / mg and was approximately 7 times larger than those of Bp adsorbed on the crystalline Calcium phosphates. TG-DTA measurements of a Bp-calcium and the composite indicated exothermic peaks due to Bp combustion, of which temperature were shifted to higher temperature for the composite. Bp in the composites was gradually released into phosphate buffered saline, while Bp was rapidly released into acetate buffer solution accompanied with the dissolution of ACP. This result suggests that the composite of Bp and ACP has potential for a drug-carrier releasing Bp in response to the condition of osteoclastic bone resorption. INTRODUCTION Recently, the number of the patients who suffer from osteoporosis has increased in step with the aging of the population. Bisphosphonate (Bp) has been used to treat osteoporosis because Bp decrease bone resorption by altering osteoclast function [1, 2]. Bp is characterized by two phosphate groups attached to a single carbon atom and has strong affinity for Ca2+ ions of bone apatite. Bp often reacts Ca2+ ions to form Bp-calcium [3]. (1) The oral administration of Bp often causes severe side effects such as osteonecrosis of the jaw [4]. As a solution for this problem, a novel treatment method that uses drug carriers is attracting a great deal of attention. Drug delivery system (DDS) has been widely investigated from clinical and material-engineering to reduce side effects and to improve efficacy of drugs. The ideal administration of a drug is to deliver a required amount of the drug to a necessary organ for an effective term. Calcium phosphate (CP) is a biocompatible carrier with high affinity for proteins and other drugs such as Bp [5]. Hydroxyapatite (HAp: Ca10(PO4)6(OH)2) is a main component of bone and is used for a bone-substituted material. HAp is known as an excellent adsorbent for organic molecules. On the other hand, octacalcium phosphate (OCP: Ca8(HPO4)2(PO4)4·5H2O) and dicalcium phosphate dehydrate (DCPD: CaHPO4·2H2O) have been known as a precursor of bone mineral, which are also thought to be one of candidates for the drug carriers. There are two kinds of drug carriers consisting of CP; one is a method of making Bp adsorbed on the surface of CP (Bp-CP) and another is a m
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