万古霉素壳聚糖微球-大孔磷酸钙骨水泥支架的体外释放实验  

In vitro sustained drug release of large-pore calcium phosphate cement and chitosan microsphere composites

作　　者：张姝江[1] 李益丰[1] 陈艺[1] 白波[1] 姚咏嫦[1] 钱东阳[1] 施雪涛[2] 王英[1] 

机构地区：[1]广州医科大学附属第一医院广东省骨科矫形技术与植入材料重点实验室,510120 [2]华南理工大学材料学院,广州510000

出　　处：《中华关节外科杂志（电子版）》2016年第6期40-45,共6页Chinese Journal of Joint Surgery(Electronic Edition)

基　　金：国家自然科学基金(81371978);广东省自然科学基金杰出青年项目(2016A030306018);广东省科技厅项目(2014A020212341)

摘　　要：目的构建具有缓释药物效能的大孔磷酸钙骨水泥(CPC)支架,并检测其药物缓释能力和对材料力学的变化。方法以乳化化学交联法制备万古霉素壳聚糖(CS)载药微球并测定药物包封率;CPC与不同质量载药微球(2 mg、6 mg、10 mg)混合制备CS-大孔CPC支架,测定载药微球-CPC的药物缓释曲线,并选择初始与8、72、168、216 h共5个时间点比较药物释放浓度。万能试验机检测载药CS-CPC支架的弹性模量变化。药物释放浓度比较和弹性模量采用单因素方差分析进行比较。结果 CS微球对万古霉素包封率约为30.6%;加入不同量的CS微球对弹性模量无明显改变,差异无统计学意义(P>0.05)。2 mg、6 mg、10 mg的CS微球与大孔CPC复合后,均能缓慢稳定释放药物。初始、8 h、72 h、168 h时间点比较药物释放浓度,三组的浓度差异有统计学意义(F=234.91,7171.27,1161569,60.5;P<0.05),其中6 mg组与2 mg和10 mg组的差异有统计学意义(P<0.05);到216 h时,各组药物浓度差异均无统计学意义(P>0.05)。结论万古霉素CS微球复合大孔CPC支架具有较为理想的药物缓释效果,并对支架的力学性能影响不大,是一种可选择的治疗骨缺损伴感染的载药材料。Objective To construct a large-pore scaffold of calcium phosphates cement （CP） as drug controlled release carrier with ability of inducing osteogenesis. Methods The vancomycin-chitosan microspheres were prepared by emulsion chemical crosslink method, and the drug loading efficiency was determined. The different amount （2 mg, 6 mg, 10 mg as three groups） of vancomycin-chitosan microspheres were mixed with CPC to make the large-pore CPC composites; the drug releasing curve was determined and five time points （0 h, 8 h, 72 h, 168 h, 216 h） were chosen to compare the drug releasing concentration of the three groups. The elastic modulus was determined and compared among the large-pore CPC composites with different amount of chitosan microspheres （0 mg, 2 mg, 6 mg, 10 mg）. The data were analyzed by one-way ANOVA. Results The drug loading efficiency of chitosan microspheres was 30. 6% ; the elastic modulus of large-pore CPC composites with different amount of chitosan spheres showed no significant difference （P 〉 0. 05 ）. The CPC composites with different amount of chitosan spheres all presented stable and slow drug releasing curves. The drug releasing concentration of the three groups at 0 h, 8 h,72 h, 168 h showed significant differences among the groups（F =234. 91, 7171.27, 1161569,60. 5, P 〈0.05） , while at 216h the differences of the three groups were not significant （P 〉0. 05）. The group of 6mg presented significant differences in drug releasing concentration at Oh, 8h,72h, 168h compare with the groups of 2mg and 6mg （ all P 〈 0. 05 ）. Conclusion The composites of vancomycin-chitosan microshperes and large-pore CPC has a stable and effective drug controlled release ability, and the chitosan microspheres show little influence on the mechanical property of CPC, which might be a potential drug controlled release carrier for bone defection with infection.

关 键 词：磷酸钙 药物缓释系统 壳聚糖 微球 

分 类 号：R68[医药卫生—骨科学] R318.08[医药卫生—外科学]