范积平,沙建平,胡艳,陈晓文,马红英,熊丹
FAN Jiping,SHA Jianping,HU Yan,CHEN Xiaowen,MA Hongying,XIONG dan

• 1:解放军第421中心医院药剂科
• 2:解放军第421中心医院内分泌科

摘要(Abstract)：

目的以Fe3O4、壳聚糖为载体制备口服胰岛新生相关蛋白磁性纳米微粒。方法通过系统考察制备材料水溶液的流动性、黏稠度、稳定性等结果确定了CTS浓度为1%、植物油与CTS乳液配比为2∶8,以Ca Cl溶液反滴滴定法等方法为INGAPMS制备工艺参数及程序。结果制备出平均粒径为3.33μm壳聚糖-Fe3O4包裹的胰岛新生相关蛋白磁性纳米微粒,其平均载药量为31.5%,平均药物包封率为91.0%。电镜观察所得MS表面光整、大小均一,体外释药实验结果显示此INGAP-MS具有良好的缓释功能,最长释药时间可达到2 d以上,大鼠经口服胰岛新生相关蛋白磁性纳米微粒后,其降糖作用可持续2 d,空腹血糖维持正常。结论口服胰岛新生相关蛋白磁性纳米微粒在药物的吸收相具有良好的量效关系,分别3H-TdR和FITC标记进行INGAP-MS体内靶向实验分析,发现INGAP-MS主要靶向至胰腺组织并能够被巨噬细胞吞噬,药效优于相同剂量的胰岛素注射剂(P<0.05)。
OBJECTIVE To prepare oral dosage form of islet neogenesis associated protein magnetic nanoparticles with Fe3O4 and chitosan. METHODS CTS at 1% concentration,plant oil and CTS latex at 2∶ 8 ratio and Ca Cl solution inverse titration as appropriate ingredients and methods for the production of INGAP-MS were identified by liquidity,viscosity and stability study of solutions.RESULTS The islet neogenesis associated protein magnetic nanoparticles were produced,wrapped around by chitosan-Fe3O4,with an average particle diameter of 3. 33 μm. Its average drug loading rate was 31. 5%,and average drug encapsulation rate was 91. 0%.In vitro drug release experiment shows that the INGAP-MS was a good mechanism of sustained release,which lasted for over 2 d. Oral administration of islet neogenesis associated protein magnetic nanoparticles on rats resulted in hypoglycemic effect for 2 d with normal fasting glucose. CONCLUSION There is good dose-response relation with regards to drug absorption for the oral islet neogenesis associated protein magnetic nanoparticles. In vivo examination with3H-TdR- and FITC-labeled INGAP-MS reveals that INGAP-MS mostly targets pancreas and is engulfed by macrophage. INGAP-MS manifests better efficacy than insulin injection of the same dose( P< 0. 05).

关键词(KeyWords)： 胰岛新生相关蛋白;磁性纳米微粒;糖尿病;靶向缓释
islet neogenesis associated protein;magnetic nanoparticles;diabetes mellitus;targeted and sustained release

Abstract:

Keywords:

基金项目(Foundation): 广东省医院药学研究基金(2014A21)

作者(Author): 范积平,沙建平,胡艳,陈晓文,马红英,熊丹
FAN Jiping,SHA Jianping,HU Yan,CHEN Xiaowen,MA Hongying,XIONG dan

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