能够高效穿透粘液层和杯状细胞的口服多肽递送系统

项目名称： 能够高效穿透粘液层和杯状细胞的口服多肽递送系统

项目编号： No.81202487

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 药物学、药理学

项目作者： 杨婷媛

作者单位： 中国科学院过程工程研究所

项目金额： 23万元

中文摘要： 蛋白多肽类药物口服给药系统具有很好的患者顺应性，但口服给药始终存在生物利用度低的难题。本研究拟采用本课题组特色的快速膜乳化技术，制备粒径均一的能够穿透粘液层和杯状细胞的载多肽类药物的PLGA/硬脂胺（SA）纳微球用于口服给药的研究。与单独使用PLGA制备的纳微球相比，SA的加入可以有效地提高亲水性小分子多肽药物的包埋率，降低药物的突释。并在纳微球表面进行PEG和CSKSSDYQC(CSK)多肽的双修饰：PEG链的修饰可以使纳微球穿透粘液层，使纳微球到达肠道上皮细胞表面；CSK多肽与肠道上皮细胞中的第二大群体杯状细胞具有很好的亲和性，CSK多肽的修饰可以改善载体跨肠道粘膜层的转运效率。因此，该递送系统有望提高多肽类药物的口服生物利用度。同时，借助于快速膜乳化制备出的不同粒径的均一纳微球，进一步探讨纳微球的粒径与口服生物利用度之间的关系，以获得最佳的口服吸收效果。

中文关键词： 粘液层；杯状细胞；口服；多肽；递送系统

英文摘要： Protein and peptide oral delivery system has a very good patient compliance, however, low oral bioavailability is still a bottleneck to be resolved. The study is to prepare uniform-sized PEG and CSKSSDYQC(CSK) peptide double-modified nano/microspheres with ability of penetrating mucus barrier and goblet cell for protein and peptide oral administration. The nano/microspheres were prepared by rapid membrane emulsification technique. We choose PLGA and stearylamine(SA) as complex preparation materials to construct the targeted carriers. Compared with single PLGA prepared nano/microspheres, the poor entrapment efficiency because of the excessive hydrophilicity of small molecular peptide and the burst release of nano/microspheres could be both improved. The surface of nano/microspheres was modified by PEG and CSKSSDYQC-peptide. The modifications of PEG make nano/microspheres penetrate mucus and increase the contact with intestinal epithelial cells; CSKSSDYQC-peptide was identified to have good affinity with the goblet cell which is the second largest population of intestinal epithelial cells. CSK peptide could prominently improve the transport efficiency of macromolecules across the intestinal mucosal barrier. Therefore, the constructed peptide delivery system may exhibit promising potential for increasing oral bioav

英文关键词： mucus；goblet cell；oral；peptide；delivery system