双氯芬酸钠丝素蛋白-壳聚糖缓释微球的制备及体内外评价  

Studies on Preparation of Diclofenac Sodium Silk Fibroin-Chitosan Sustained-Release Microsphere and Its Characteristics in Vivo and in Vitro

作　　者：刘纯[1] 金梦瑶[1] 张学农[1,2] 

机构地区：[1]苏州大学药学院,江苏苏州215123 [2]苏州利元医药科技有限公司,江苏苏州215002

出　　处：《中国药学杂志》2009年第21期1642-1647,共6页Chinese Pharmaceutical Journal

基　　金：国家科技支撑计划课题资助(2006BAI09B00);国家科技部科技型中小企业技术创新基金(07C26223201333);江苏省高校高新技术产业发展项目资助(JHB05-46);江苏省“六大人才高峰”资助项目;江苏省卫生厅招标项目(H200630)

摘　　要：目的以双氯芬酸钠(diclofenac sodium,DS)为模型药物,丝素蛋白(silk fibroin,SF)/壳聚糖(chitosan,CS)(1∶1)为复合载体制备双氯芬酸钠丝素蛋白/壳聚糖缓释微球(DS-SF/CS-MS),并考察其体内外相关性。方法采用乳化-化学交联固化法制备DS-SF/CS-MS;动态透析法考察了微球的体外释放特性;以DS溶液对照,大鼠分别ig相同剂量的DS-CS-MS和DS-SF/CS-MS后,HPLC测定血浆中DS浓度,3P97程序计算药动学参数。结果DS-SF/CS-MS的载药量和包封率分别为(9.88±0.49)%和(50.35±0.92)%,平均粒径为(26.54±1.39)μm;DS-SF/CS-MS在不同pH的释放介质中均遵循Higuchi方程,其缓释效果明显优于双氯芬酸钠-壳聚糖微球(DS-CS-MS);大鼠体内的双氯芬酸钠血药浓度经时曲线均符合一室模型,3种制剂的MRT分别为(4.11±0.03),(6.92±0.39)和(24.35±0.27)h。DS-SF/CS-MS的MRT与t1/2明显延长,其相对生物利用度为溶液剂的140.0%。结论SF/CS-MS的性能优异,有望成为一种低毒性的新型缓控释载体材料。OBJECTIVE To study preparation and pharmaceutical characteristics of diclofenac sodium loaded silk fibroin-chitosan microspheres（DS-SF/CS-MS） in vitro and in vitro. METHODS DS-SF/CS-MS were prepared with an emulsion crosslinking technique. Dynamic dialysis system was adopted to study the release dynamics of DS-SF/CS-MS in vitro. SD rats were used as the animal model. DS concentration in plasma was determined by HPLC after the intragastric administration of DS-CS-MS and DS-SF/CS-MS with same dose. Its pharmacokinetic parameters were calculated by 3P97 program. RESULTS The loading drug content and encapsulated efficiency of the microspheres were （9.88±0.49） % and （50.35±0.92）%, respectively. Its average diameter was about （26.54±1.39）μm. The release of DS-SF/CS-MS followed Higuchi＇s equation in PBS with different pH value. The slow-release property of DS-SF/CS-MS was better than that of the chitosan microspheres. The plasma concentration versus time curve was coincident with one compartment model. MRTs of the three formulation were （4.11±0.03）, （6.92±0.39） and （24.35±0.27）h, respectively. Compared with DS solution and DS-CS-MS, t1/2 of DS-SF/CS-MS was prolonged and relative bioavailability was 140.0%. CONCLUSION SF/CS-MS was a potential novel sustained-release carrier material with low toxicity.

关 键 词：丝素蛋白 壳聚糖 缓释微球 双氯芬酸钠 

分 类 号：R944[医药卫生—药剂学]