京尼平与戊二醛交联明胶微球的性能比较  

COMPARISON OF CHARACTERISTICS BETWEEN GLUTARALDEHYDE-AND GENIPIN-CROSSLINKED GELATIN MICROSPHERES

作　　者：厉孟[1] 刘旭东[1] 刘兴炎[1] 

机构地区：[1]兰州军区兰州总医院骨科兰州,730050

出　　处：《中国修复重建外科杂志》2009年第1期87-91,共5页Chinese Journal of Reparative and Reconstructive Surgery

基　　金：全军“十一五”医药卫生科研基金资助项目(06MA090);甘肃省自然科学基金资助项目(0710RJZA068)~~

摘　　要：目的比较京尼平(genipin,GP)及戊二醛(glutaraldehyde,GA)交联明胶微球的性能,探讨GP交联明胶微球的优缺点。方法以改进的双相乳化冷凝聚合法制备明胶微球,分别以GP、GA进行交联。取60%交联度的GP及GA明胶微球,分散于PBS中,比较其粒径外观、溶胀及降解性能。两种交联明胶微球分别携载rhBMP-2,测定载药量及包封率,观察10d内的药物缓释性能。收集GP及GA明胶微球浸提液,倍比稀释成100%、50%、25%浓度,分别与小鼠成骨细胞共培养2d,以DMEM组为阴性对照组,MTT法检测细胞增殖,测定GP及GA微球的细胞毒性。结果GP及GA交联明胶微球在溶液中均呈规则圆形,粒径分别为(78±18)、(65±10)μm,GP交联明胶微球分散性更佳。当交联度均为60%时,GP交联明胶微球溶胀率为89.0%±4.8%,显著低于GA交联明胶微球(118.0%±7.6%),差异有统计学意义(P<0.01);GP及GA交联明胶微球分别于28、21d完全降解,两者比较差异有统计学意义(P<0.05)。GP及GA交联明胶微球载药量分别为(921±73)、(965±62)ng/g,包封率分别为88.5%±2.1%、89.7%±1.8%,两者比较差异均无统计学意义(P>0.05)。GP及GA交联明胶微球10d累积释药百分率分别为78.80%±4.96%、90.50%±5.12%,两者比较差异有统计学意义(P<0.05)。当浸提液浓度为25%、50%、100%时,GP交联明胶微球细胞毒性均为Ⅰ级,GA交联明胶微球细胞毒性分别为Ⅱ、Ⅲ、Ⅲ级。结论与GA交联明胶微球比较,GP交联明胶微球的综合性能更优越,可应用于组织工程领域。or genipin （GP） Objective To compare the characteristics of gelatin microspheres crosslinked by glutaraldehyde （GA） Methods Gelatin microspheres, prepared by the improved emulsified cold-condensation method, were crosslinked by GP and GA, respectively. After being dispersed in PBS, two kinds of microspheres with 60% degree of cross linking were compared in terms of morphology, swelling and degrading properties, rhBMP-2 were loaded into the GP and GA microspheres, and the encapsulation rate, drug loading and releasing capacity were measured; 100%, 50% and 25% leaching liquid of GP and GA microspheres were respectively cultured with rat osteoblast （DMEM group as the control）, and cell proliferation was measured by MTT method to grade the cell cytotoxicity. Results GP and GA microspheres were both spherical with the diameters of （78 ± 18） μm and （65 ± 10） μm, and there were no difference between both microspheres in drug loading and encapsulation rate. But, GP microspheres, with long degrading period （28 days） compared to GA microspheres （21 days）, had better dispersibility, and swelling rate （89.0% ± 4.8%）, the percentage of cumulative drug releasing at 10 days （78.80% ± 4.96%） were both lower than GA microsphere （118.0% ± 7.6%, 90.50% ± 5.12%）. The percentages of drug loading of GP and GA were （921 ± 73） and （965 ± 62） ng/g, and the encapsulation rates were 88.5% ± 2.1% and 89.7% ± 1.8%; showing no significant difference （P 〉 0.05）. The cell cytotoxicity of 100%, 50% and 25% leaching liquid of GP microspheres was all at the level I, but leaching liquid of GA microspheres with corresponding concentration were at the levels of Ⅲ、Ⅲ and Ⅱ. Conclusion GP crosslinked gelatin microspheres are superior to GA crosslinked gelatin microspheres and can be widely used in tissue engineering field.

关 键 词：骨组织工程 京尼平 戊二醛 明胶微球 比较 

分 类 号：R318[医药卫生—生物医学工程] R318.08[医药卫生—基础医学]