载药型磷酸钙骨水泥的制备及体外释放性能

Preparation and in vitro release properties of drug-loaded calcium phosphate cement

背景:磷酸钙骨水泥具有良好的生物相容性,可作为骨修复材料与药物载体。目的:制备载药磷酸三钙骨水泥,并分析其体外释放性能。方法:采用共沉淀法制备磷酸三钙前躯体,经高温煅烧研磨获得α-磷酸三钙粉体,测试含不同浓度(1.25%,2.5%,3.75%,5%)抗生素(头孢拉定或头孢氨苄或环丙沙星)骨水泥,浸泡不同时间后(6h、12h、24h、2d、3d、4d、5d、6d、7d、8d)的药物体外释放浓度。结果与结论:制备的磷酸三钙粉体粒度约2μm,结晶度良好。载不同抗生素的骨水泥体外释放都受自身物理性质的影响。载药骨水泥中环丙沙星能够满足长时间缓释,并能达到一个比较理想的缓释浓度,头孢类药物由于自身稳定性等原因,缓释效果并不理想。头孢氨苄的水解速率较低,环丙沙星的光降解条件比较苛刻,因此两者释放未受太大影响,与Higuchi模型基本吻合;头孢拉定的水解速率相对较高,对体系的释放驱动力产生较大影响,使得释放不再遵循Higuchi模型。

BACKGROUND： Calcium phosphate cement cannot only be used as a bone repair material but also serve as drug carriers due to its good biocompatibility. OBJECTIVE： To prepare drug-loaded tricalcium phosphate （TCP） bone cement, and to analyze its in vitro release properties. METHODS： First, TCP precursor powder was prepared by co-precipitation method. Second, a-TCP was obtained after it was powdered at high temperature. Then, in vitro drug release concentrations of bone cement with 1.25%, 2.5%, 3.75% and 5% antibiotics （cefradine, cephalexin or ciprofloxacin） after different soaking time （6 hours, 12 hours, 24 hours, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days and 8 days） were tested. RESULTS AND CONCLUSION： The particle size of TCP power prepared by co-precipitation was about 2 pm, and it had good crystallinity. In vitro releases of bone cement loaded with cephalexin, cefradine and ciprofloxacin were subject to their physical properties. Bone cement loaded with ciprofloxacin could meet long-time release and reach a more ideal release concentration. The release effect of cephalosporin drugs was not very good due to their stability and other reasons. While, cephalexin hydrolysis rate was low, and the photodegradation of ciprofloxacin was in relatively harsh conditions, so their release was not affected, which was basically consistent with the Higuchi model. But cefradine hydrolysis rate was relatively higher, and the system release driving force was much affected, which could cause the release no longer follow the Higuchi model.