中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
  4. 药物制剂研究中心
Transport mechanism of lipid covered saquinavir pure drug nanoparticles in intestinal epithelium

文献类型：期刊论文

作者Xia, Dengning2,6; He, Yuan1,2; Li, Qiuxia1,2; Hu, Cunde2,3; Huang, Wei4; Zhang, Yunhai4; Wan, Feng5; Wang, Chi1; Gan, Yong2
刊名JOURNAL OF CONTROLLED RELEASE
出版日期2018-01-10
卷号269页码:159-170
ISSN号0168-3659
关键词Surface modification Phospholipid bilayer Nanodrug Endocytosis Transcytosis P-type glycoprotein substrate
DOI10.1016/j.jconrel.2017.11.012
文献子类Article
英文摘要Pure drug nanoparticles (NPs) represent a promising formulation for improved drug solubility and controlled dissolution velocity. However, limited absorption by the intestinal epithelium remains challenge to their clinical application, and little is known about how these NPs within the cells are transported. To improve cellular uptake and transport of pure nanodrug in cells, here, a lipid covered saquinavir (SQV) pure drug NP (Lipo@nanodrug) was designed by modifying a pure SQV NP (nanodrug) with a phospholipid bilayer. We studied their endocytosis, intracellular trafficking mechanism using Caco-2 cell model. Uptake of Lipo@nanodrug by Caco-2 cells was 1.91-fold greater than that of pure nanodrug via processes involving cell lipid raft. The transcellular transport of Lipo@nanodrug across Caco-2 monolayers was 3.75-fold and 1.92-fold higher than that of coarse crystals and pure nanodrug, respectively. Within cells, Lipo@nanodrug was mainly localized in the endoplasmic reticulum and Golgi apparatus, leading to transcytosis of Lipo@nanodrug across intestinal epithelial cells, whereas pure nanodrug tended to be retained and to dissolve in cell and removed by P-gp-mediated efflux. In rats, the oral bioavailability of the model drug SQV after Lipo@nanodrug administration was 4.29-fold and 1.77-fold greater than after coarse crystal and pure nanodrug administration, respectively. In conclusion, addition of a phospholipid bilayer to pure drug NP increased their cellular uptake and altered their intracellular processing, helping to improve drug transport across intestinal epithelium. To our knowledge, this is the first presentation of the novel phospholipid bilayer covered SQV pure drug NP design, and a mechanistic study on intracellular trafficking in in vitro cell models has been described. The findings provide a new platform for oral delivery of poorly water-soluble drugs.
WOS关键词VITAMIN-E TPGS ; P-GLYCOPROTEIN ; ORAL DELIVERY ; CELLULAR UPTAKE ; INTRACELLULAR-TRANSPORT ; POLYMER NANOPARTICLES ; SILICA NANOPARTICLES ; CELLS ; NANOCRYSTALS ; ENDOCYTOSIS
资助项目National Natural Science Foundations of China[81673379] ; National Natural Science Foundations of China[81202468] ; China Postdoctoral Science Foundations[2014T70445] ; Chinese Academy of Sciences[CASIMM0120163016] ; Youth Innovation Promotion Association-CAS[2017336] ; Shanghai Science and Technology Innovation Action Plan for Basic Research[14JC1493200]
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
出版者ELSEVIER SCIENCE BV
WOS记录号WOS:000423760400015
源URL[http://119.78.100.183/handle/2S10ELR8/272286]  
专题药物制剂研究中心
通讯作者Xia, Dengning; Gan, Yong
作者单位1.Chongqing Med Univ, Sch Pharm, Chongqing 400016, Peoples R China;
2.Chinese Acad Sci, Shanghai Inst Mat Med, 501 Haike Rd, Shanghai 201203, Peoples R China;
3.Univ Sci & Technol China, Nano Sci & Technol Inst, 166 Renai Rd, Suzhou 215123, Jiangsu, Peoples R China;
4.Chinese Acad Sci, Jiangsu Key Lab Med Opt, Suzhou Inst Biomed Engn & Technol, Suzhou 215163, Peoples R China;
5.Univ Copenhagen, Fac Hlth & Med Sci, Dept Pharm, Univ Pk 2, DK-2100 Copenhagen, Denmark;
6.Georgia Inst Technol, Sch Chem & Biomol Engn, Atlanta, GA 30332 USA
推荐引用方式
GB/T 7714		 Xia, Dengning,He, Yuan,Li, Qiuxia,et al. Transport mechanism of lipid covered saquinavir pure drug nanoparticles in intestinal epithelium[J]. JOURNAL OF CONTROLLED RELEASE,2018,269:159-170.
APA Xia, Dengning.,He, Yuan.,Li, Qiuxia.,Hu, Cunde.,Huang, Wei.,...&Gan, Yong.(2018).Transport mechanism of lipid covered saquinavir pure drug nanoparticles in intestinal epithelium.JOURNAL OF CONTROLLED RELEASE,269,159-170.
MLA Xia, Dengning,et al."Transport mechanism of lipid covered saquinavir pure drug nanoparticles in intestinal epithelium".JOURNAL OF CONTROLLED RELEASE 269(2018):159-170.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。