含甲氨喋呤的磷酸钙骨水泥药物释放体系的制备及体外药物释放

Development of a Novel Drug Dilivery System Based on Calcium Phosphate Cement with Methotrexate and Its Drug Release Test in vitro

目的观察含甲氨喋呤(MTX)的磷酸钙骨水泥(CPC)的药物释放体系在体外模拟体液中的药物释放情况。方法将MTX与CPC分别以0.1%、0.2%、0.5%质量分数混合,固化后放于37℃恒温模拟体液中,分别于2、5、10、16h、1、2、3、5、8、10、15、20、25、30、35、40、45d用高效液相色谱法测定模拟体液中MTX的浓度,绘制药物释放-时间曲线,分析药物释放规律。结果MTX-CPC复合物在模拟体液中的MTX释放缓慢而稳定,释放前期有明显的缓冲释放效应,符合Higuchi模型的药物释放规律。MTX释放浓度及速度与MTX在骨水泥中的包埋量有关,与骨水泥的厚度及形状无关。MTX的释放周期不受所含MTX量的影响。结论以CPC为载体,将MTX以适当浓度包埋,可制成稳定的药物释放体系。

Objective To develop a novel drug dilivery system based on calcium phosphate cement （CPC） with methotrexate （MTX） as a model drug and to study its drug release in vitro. Methods Three MTX mass fractions （0. 1% , 0. 2% , and 0. 5% ） were tested after solidification, and the compound of CPC- MTX were put into the simulated body fluid at 37℃. The concentration of MTX was tested by high-performance liquid chromatography at day 2, 5, 10, 16 hours, 1, 2, 3, 5, 8, 10, 15, 20, 25, 30, 35, 40, and 45 days. The drug dilivery curves were drawn and drug dilivery rules were analyzed. Results MTX was released slowly and stably from the compound of CPC-MTX. Remarked prophase of drug release was noted, which conformed with the Higuchi equation. The drug release rate and concentration was related with the concentrafion of MTX in compound but not with the thickness and shape of CPC. The releasing time was not affected by the concentration of MTX. Conclusion A stable drug dilivery system can be developed by loading proper concentration of MTX into CPC.