Transport mechanism of lipid covered saquinavir pure drug nanoparticles in intestinal epithelium
| Autor: | Feng Wan, Dengning Xia, Yuan He, Yunhai Zhang, Yong Gan, Cunde Hu, Chi Wang, Qiuxia Li, Wei Huang |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Administration Oral Biological Availability Pharmaceutical Science 02 engineering and technology Endocytosis Rats Sprague-Dawley 03 medical and health sciences Intestinal mucosa Animals Humans Intestinal Mucosa Lipid bilayer Lipid raft Phospholipids Saquinavir Chemistry Biological Transport HIV Protease Inhibitors 021001 nanoscience & nanotechnology Intestinal epithelium 030104 developmental biology Biochemistry Transcytosis Paracellular transport Biophysics Nanoparticles Caco-2 Cells 0210 nano-technology Intracellular |
| Zdroj: | Journal of Controlled Release. 269:159-170 |
| ISSN: | 0168-3659 |
| DOI: | 10.1016/j.jconrel.2017.11.012 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect