单因素试验筛选缓释碱性成纤维细胞生长因子微球的制备条件  

Optimal preparative conditions for screening basic fibroblast growth factor controlled release microspheres using single factor design

作　　者：段宏[1] 樊瑜波[2,3] 屠重棋[1] 刘钰[4] 裴福兴[1] 

机构地区：[1]四川大学华西医院骨科,四川省成都市610041 [2]北京航空航天大学生物工程系,北京市100083 [3]四川大学建筑与环境学院生物力学工程实验室,四川省成都市610065 [4]中国科学院成都有机化学研究所,四川省成都市610041

出　　处：《中国组织工程研究与临床康复》2008年第49期9664-9668,共5页Journal of Clinical Rehabilitative Tissue Engineering Research

基　　金：国家自然科学基金资助项目(10402025)~~

摘　　要：背景:研究表明,缓释碱性成纤维细胞生长因子微球制备工艺条件影响因素多,筛选工作费时费力,且工艺的重现性较差。目的:以碱性成纤维细胞生长因子包封率为指标,应用单因素设计,初步考察碱性成纤维细胞生长因子缓释微球制备基本工艺条件。设计、时间及地点:单因素设计实验,于2005-03/05在中国科学院成都有机化学研究所高分子实验室完成。材料:以相对分子质量2.0万聚乳酸-羟基乙酸共聚物为载体材料,选用W/O/W复乳-干燥法制备碱性成纤维细胞生长因子-聚乳酸-羟基乙酸共聚物微球。方法:应用单因素设计,初选匀化方式(超声或旋涡)、超声时间(第1次+第2次:5s+5s,5s+10s,10s+5s,10s+10s)、内水相体积(50,100,200,250,300μL)、分散介质聚乙烯醇质量浓度(10,20,30,50,70g/L)、外水相中无机盐浓度(0,250,500,1000g/L)、搅拌时间(3,4,5,6,8h)等缓释微球制备基本工艺条件。主要观察指标:各制备工艺条件下微球粒径、载药量和包封率。结果:单因素试验结果表明,制备碱性成纤维细胞生长因子微球时,超声时间和搅拌时间对于包封率没有影响;匀化方式应选择2次超声,每次5s;聚乙烯醇质量浓度在30～70g/L内较好;内水相体积可固定在50～100μL;外水相中无机盐的浓度越高越好,还可进一步筛选出最佳浓度。经过初步优化后,其平均粒径为6.68μm,径距为(1.86±0.22)μm,载药量为(37.00±0.89)×10-3%,包封率为(61.31±1.31)%。结论:应用单因素试验可以初步优选碱性成纤维细胞生长因子缓释微球制备工艺条件。BACKGROUND： The preparative conditions for basic fibroblast growth factor （bFGF） controlled release microspheres affected by various factors, which was hard to optimization. OBJECTIVE： Take entrapment efficiency as evaluating index, to evaluate the preparative conditions for bFGF controlled release microspheres, which were optimized in accordance with single factor design. DESIGN, TIME AND SETTING： The single factor design was performed in the Macromolecule Laboratory, Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences from March to May in 2005. MATERIALS： The bFGF controlled release microspheres were prepared by W/O/W multiple emulsions volatilizing method with poly （lactic-co-glycolic acid） （PLGA, Mt 20 000）. METHODS： The different preparative conditions, such as homogenization method, ultrasonic time, volume of inner-phase, concentration of polyvinyl alcohol, concentration of the inorganic salt in the outer-aqueous phase, different stirring time, were optimized by single factor design. MAIN OUTCOME MEASURES： The microsphere size, drug loading entrapment efficiency and entrapment efficiency were evaluated under different preparative conditions. RESULTS： The outcome of single factor design demonstrated that the ultrasonic time and stirring time had no significantly effect on the entrapment n efficiency. However, the bFGF microspheres made by ultrasonic twice with 5 second each time, with 50-100μL volume of inner-phase, 3%-7% concentration of PVA, and the higher the concentration of the inorganic salt in the outer-aqueous the better. After optimization, the mean particle size of bFGF microspheres was mean 6.68 μ m and 1.86 ± 0.22 of size span, with the drug loading volume and entrapment efficiency of （37.00 ±0.89） ×10 3 % and （61.31±1.31） %, respectively. CONCLUSION： The primarily preparative conditions for bFGF controlled release microspheres can be investigated by single factor design.

关 键 词：碱性成纤维细胞生长因子 聚乳酸-聚羟基乙酸共聚物 微球 缓释 单因素设计 

分 类 号：R318[医药卫生—生物医学工程]