摘要
采用正交试验法优化载转化生长因子β1(transforming growth factor-β1,TGF-β1)缓释明胶微球多孔钛植入体制备工艺,探讨多孔钛植入体孔隙内微球涂层的载药、释药特性。采用粉末注射成形(Metal Injection Molding,MIM)技术制备多孔钛植入体,选用明胶为TGF-β1缓释载体材料,乳化冷凝聚合交联法制备明胶微球,检测微球粒径与形貌以及载TGF-β1微球的包封率、载药率,采用渗涂法制备多孔钛表层孔隙内载TGF-β1明胶微球涂层,释放试验检测涂层的释药特性。实验结果表明,MIM技术制备的多孔钛植入体的孔隙度为(62.02±1.82)%,孔径为50~300μm,抗压缩强度为(63.23±12.81)MPa,弹性模量为(0.95±0.61)GPa。明胶微球粒径随明胶浓度的减小、搅拌速度和交联时间的增加而减小,交联剂用量对微球粒径影响无显著性差异。制备的TGF-β1明胶微球为球形,平均粒径为(21.42±3.67)μm,载药量为(0.91±0.02)μg/g,包封率为(91.41±1.82)%。TGF-β1微球涂层体外14d,时的TGF-β1释放率为(94.2±3.4)%;粒径为(21.42±3.67)μm的明胶微球的最佳工艺参数如下:明胶浓度为10%,搅拌速度为800r/min,交联剂用量为0.1mL,交联时间为2h。多孔钛植入经5%(质量分数)明胶溶液预处理后用20g/L微球渗涂可在表层孔隙内形成均匀微球涂层,且不阻塞表层孔隙,微球涂层TGF-β1释放时间为14d。
The effects of process parameters on the preparation of porous titanium coated with TGF-β1 loaded gelatin microspheres were systematically studied by orthogonal arrays design and statistical analysis method.Porous titanium implants with porosity of 60%were prepared by metal injection molding.Gelatin microspheres were prepared by improved emulsified cold condensation method and loaded with TGF-β1 by swelling in aqueous TGF-β1 solution.The morphology of the microspheres were observed by scanning electron microscopic(SEM).The encapsulation rate and drug content were tested with TGF-β1 ELISA kit.The porous titanium implants were coated with TGF-β1 loaded gelatin microspheres and characterized by drug release kinetics.The results show that the porosity and pore size of porous titanium implants are(62.02±1.82)%and 50 300μm,respectively.The compression yield strength is(49.21±10.81)MPa,and elastic modulus is(5.81±1.32)GPa.The diameter of gelatin microspheres decreases with the decrease ofgelatin concentration and the increase of stirring speed and cross-linking time.However,cross-linking agent has no distinguished influence on the diameter.The diameter of gelatin microspheres is(21.42±3.67)μm in average.The drug content is(0.91±0.02)μg/g,and encapsulation rate is(91.41±1.82)%.In vitro,(94.2±3.4)%of TGF-β1 were released after 14 d.The optimized preparation parameters of gelatin microspheres are as follows:gelatin concentration 10%(mass fraction),stirring speed 800 r/min,cross linking agent 0.1 mL,and crosslinking time 2 h.The porous titanium implants can be coated with 5%(mass fraction)gelatin and 20 g/L TGF-β1 loaded gelatin microspheres,and the structure of pores are kept completely.In vitro,TGF-β1 can be released for 14 d.
出处
《中南大学学报(自然科学版)》
EI
CAS
CSCD
北大核心
2009年第5期1228-1234,共7页
Journal of Central South University:Science and Technology
基金
国家自然科学基金资助项目(35770576)
国家"863"计划项目(2007AA03Z114)
湖南省自然科学基金资助项目(2007JJ5109)
关键词
多孔钛
转化生长因子Β1
明胶
缓释微球
正交实验
porous titanium
transforming growth factor-β1
gelatin
microspheres
orthogonal arrays design