摘要
背景:大多数蛋白质和多肽药物存在稳定性差、生物利用度低等缺点,为提高其生物利用度,目前常用将蛋白类药物包裹在高分子材料中,制成缓释控释体系。由于蛋白质外层的载体材料能起到一定保护作用,因此可增加此类药物的稳定性。目的:以含水率为指标,通过正交实验设计,找出制备海藻酸钙微球的最佳条件。并以牛血清白蛋白为模型药物,考察微球载药性能及pH环境下的释放规律。设计、时间及地点:对比观察实验,于2007-10/2009-05在四川大学高分子科学与工程实验楼完成。材料:海藻酸钠、无水氯化钙由成都科龙试剂公司提供,牛血清白蛋白由上海伯奥生物科技有限公司提供。方法:采用滴制法制备了海藻酸钙微球,考察了海藻酸钠质量分数、氯化钙质量分数、交联时间对微球含水率的影响。采用牛血清白蛋白作为模型药物,对优化条件下海藻酸钠凝胶微球进行载药量和释放行为的考察。主要观察指标:微球中牛血清白蛋白包封率及在不同pH介质中白蛋白的释放行为。结果:当海藻酸钠质量分数、氯化钙质量分数均为2.0%,交联时间为6h,所得微球含水率最高能达到70%。pH溶胀实验显示,微球在盐酸溶液,氯化钠溶液中不溶胀,而在磷酸盐缓冲液中溶胀体现一定的pH敏感性。微球载药量约为5%,包封率为70%左右。对药物释放曲线几种模型方程进行拟合,发现释放曲线不符合Higuchi释放模型。结论:滴制法制备海藻酸钠微球条件温和,不接触有机溶剂。微球含水率高具有pH敏感性且能有效载药,适合作为蛋白质和多肽药物包裹材料。
BACKGROUND： Most of protein and polypeptide drugs are usually low stability and bioavailability. For the purpose of higher bioavailability, the common method is to encapsulate the drug into polymers microspheres, which form control-released system. It also can improve drugs stability due to the polymer due to the protective effect of the coated materials. OBJECTIVE： Based on water content, the preparation of microspheres was optimized by the orthogonal experiments. The drug loading efficiency as well as drug release in different pH was studied by using bovine serum albumin as a model protein drug. DESIGN, TIME AND SETTING： The contrast observation experiment was performed at the Department of Polymer Science and Engineering, Sichuan University from October 2007 to May 2009. MATERIALS： Sodium alginate and calcium chloride were provided by Kelong Reagent Company, Bovine serum albumin was obtained from Shanghai Boao Biological Technology Company. METHODS： Alginate microspheres were prepared by dropping in the experiment. The impact of experimental condition such as the concentration of sodium alginate, calcium chloride concentration and the cross-linked time to water content were investigated. In vitro release behavior of the microspheres was studied in different pH value medium. MAIN OUTCOME MEASURES： The entrapment efficiency, as well as bovine serum albumin release in different pH value medium. RESULTS： The optimum preparation conditions were selected： the sodium alginate and calcium chloride mass fraction were 2.0%, respectively, the cross-linked time was 6 hours. The water content was 70% maximally. The microspheres swell in phosphate buffer （pH7.4） exhibited pH responsiveness properties. The drug loading efficiency was approximately 5%, and the drug encapsulation efficiency was about 70%. The bovine serum albumin release data were analyzed according to zero-order and first-order kinetics as well as the Higuchi model using linear regreession analysis. The results revealed that bovine serum albumin release from phosphate buffer did not fit Higuchi diffusion. CONCLUSION： Alginate provides mild preparation condition without organic solvent. It is a promising system for controlled release drug delivery carrier due to high water content and pH-sensitive release.
出处
《中国组织工程研究与临床康复》
CAS
CSCD
北大核心
2009年第42期8303-8306,共4页
Journal of Clinical Rehabilitative Tissue Engineering Research
