β-磷酸三钙/聚乳酸-聚羟基乙酸/异烟肼缓释材料制备与分析  

Preparation and evaluation of poly(lactic-co-glycolic acid)/β-tricalcium phosphate/isoniazid slow-release material in animal model

作　　者：李大伟 马远征 杨飞[2] 崔旭 李力韬 安晋宇 张嘉利 

机构地区：[1]解放军第三○九医院全军骨科中心,北京100091 [2]中国科学院化学所高分子物理与化学国家重点实验室

出　　处：《中国防痨杂志》2013年第5期309-313,共5页Chinese Journal of Antituberculosis

基　　金：国家自然科学基金(81071454)

摘　　要：目的制备β-磷酸三钙/聚乳酸-聚羟基乙酸/异烟肼缓释材料,分析材料体内外性能。方法聚乳酸-聚羟基乙酸溶解于适量1,4-二氧六环中,将β-磷酸三钙、异烟肼二种粉末直接混入PLGA溶液中,超声混合均匀。将悬浊液置入模具中制成材料。扫描电镜观察材料结构,并进行药代动力学分析。取36只新西兰大白兔,通过数字表法随机分为3组,每组12只;制作股骨髁缺损模型,分别于骨缺损处植入β-磷酸三钙/聚乳酸-聚羟基乙酸材料(β-TCP/PLGA)(实验Ⅰ组)、β-磷酸三钙/聚乳酸-聚羟基乙酸/异烟肼(β-TCP/PLGA/INH)(实验Ⅱ组)缓释材料,并设置空白对照组(实验Ⅲ组,不植入任何材料)。术后4、8和12周观察材料修复骨缺损的情况,并采用影像学、组织学评分和骨长入率评价骨修复效果。结果β-TCP/PLGA/INH缓释材料在局部可持续释放异烟肼至12周。12周后,实验Ⅰ组与Ⅱ组骨缺损得到修复,实验Ⅲ组骨缺损未修复;实验Ⅰ组和实验Ⅱ组的骨长入率分别为83.0%±7.0%、84.0%±6.0%,而实验Ⅲ组为10.0%±1.1%,组织学评分分别为(7.3±0.6)分、(7.1±0.8)分、(2.0±0.4)分。组织学评分和骨长入率在实验Ⅰ与Ⅱ组间差异不具有统计学意义(组织学评分t值为0.400,P>0.05;骨长入率:t=-0.217,P>0.05);和空白对照组间差异具有统计学意义(组织学评分t值分别为14.700、11.404,P值均<0.01;骨长入率:t值分别20.604和24.262,P值均<0.01)。结论β-磷酸三钙/聚乳酸-聚羟基乙酸/异烟肼缓释材料可很好的修复兔骨缺损,材料降解速度与骨形成速度相匹配,并能在足够成长的时间范围内维持异烟肼的释放。Objective To prepare poly（lactic-co-glycolic acid）/β-tricalcium phosphate material loaded with isoniazid and to evaluate its function in vitro and in vivo. Methods The lactic acid/glycolic acid copolymer was dissolved in 1,4-dioxane mixed with β-tricalcium phosphate and isoniazid powder to prepare a liquid slurry. The liquid slurry was mixed well-distributed under ultrasound, and then was put into a cylindrical artificial bone carrier to form the artificial bone materials. The morphology of the material was observed by electron microscopy scanning and the pharmacokinetics was analyzed with HPLC. Thirty-six New Zealand rabbits made femora condyle defects model were divided randomly into three groups（12 rabbits in each group）. Group Ⅰ： loaded in active artificial bone without isoniazid. Group Ⅱ： loaded in active artificial bone with isoniazid. Group Ⅲ： non-loaded any materials as blank control. The repair of bone defects were observed and evaluated by imaging, histological scoring, bone growth rate after 4,8 and 12 weeks of operation. Results The artificial material can release INH constantly for 12 weeks. At the 12th week, all bone defects in the experimental groups（groupⅠand group Ⅱ） were radiographically repaired. The histological scoring and bone growth rate were 7.3±0.6,7.1±0.8,2.0±0.4 and 83.0%±7.0%, 84.0%±6.0%, 10.0%±1.1% in three groups, respectively. There were significant differences between groupⅠand group Ⅲ, also in group Ⅱ and group Ⅲ among histological scoring and bone growth rate（t values of histological scoring were 14.700,11.404,P〈0.01. t values of bone growth rate were 20.604 and 24.262, P〈0.01）. But the parameters were similar in groupⅠand group Ⅱ（t values of histological scoring were 0.400,P〉0.05. t values of bone growth rate -0.217, P〉0.05）. Conclusion Poly（lactic-co-glycolicacid）/β-tricalcium phosphate/isoniazid slow-release material can effectively repair bone defects in rabbits, its degradation rate well matches the bone

关 键 词：异烟肼 药物释放系统 聚乙醇酸 乳酸 磷酸钙类 结核 脊柱 

分 类 号：R318.08[医药卫生—生物医学工程]