Transport mechanism of lipid covered saquinavir pure drug nanoparticles in intestinal epithelium

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

Transport mechanism of lipid covered saquinavir pure drug nanoparticles in intestinal epithelium. / Xia, Dengning; He, Yuan; Li, Qiuxia; Hu, Cunde; Huang, Wei; Zhang, Yunhai; Wan, Feng; Wang, Chi; Gan, Yong.

In: Journal of controlled release : official journal of the Controlled Release Society, Vol. 269, 01.2018, p. 159-170.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Xia, D, He, Y, Li, Q, Hu, C, Huang, W, Zhang, Y, Wan, F, Wang, C & Gan, Y 2018, 'Transport mechanism of lipid covered saquinavir pure drug nanoparticles in intestinal epithelium', Journal of controlled release : official journal of the Controlled Release Society, vol. 269, pp. 159-170. https://doi.org/10.1016/j.jconrel.2017.11.012

APA

Xia, D., He, Y., Li, Q., Hu, C., Huang, W., Zhang, Y., ... Gan, Y. (2018). Transport mechanism of lipid covered saquinavir pure drug nanoparticles in intestinal epithelium. Journal of controlled release : official journal of the Controlled Release Society, 269, 159-170. https://doi.org/10.1016/j.jconrel.2017.11.012

Vancouver

Xia D, He Y, Li Q, Hu C, Huang W, Zhang Y et al. Transport mechanism of lipid covered saquinavir pure drug nanoparticles in intestinal epithelium. Journal of controlled release : official journal of the Controlled Release Society. 2018 Jan;269:159-170. https://doi.org/10.1016/j.jconrel.2017.11.012

Author

Xia, Dengning ; He, Yuan ; Li, Qiuxia ; Hu, Cunde ; Huang, Wei ; Zhang, Yunhai ; Wan, Feng ; Wang, Chi ; Gan, Yong. / Transport mechanism of lipid covered saquinavir pure drug nanoparticles in intestinal epithelium. In: Journal of controlled release : official journal of the Controlled Release Society. 2018 ; Vol. 269. pp. 159-170.

Bibtex

@article{4b11c7f2cd304a138ee41ce9fd169526,
title = "Transport mechanism of lipid covered saquinavir pure drug nanoparticles in intestinal epithelium",
abstract = "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.",
keywords = "Journal Article",
author = "Dengning Xia and Yuan He and Qiuxia Li and Cunde Hu and Wei Huang and Yunhai Zhang and Feng Wan and Chi Wang and Yong Gan",
note = "Copyright {\circledC} 2017. Published by Elsevier B.V.",
year = "2018",
month = "1",
doi = "10.1016/j.jconrel.2017.11.012",
language = "English",
volume = "269",
pages = "159--170",
journal = "Journal of Controlled Release",
issn = "0168-3659",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Transport mechanism of lipid covered saquinavir pure drug nanoparticles in intestinal epithelium

AU - Xia, Dengning

AU - He, Yuan

AU - Li, Qiuxia

AU - Hu, Cunde

AU - Huang, Wei

AU - Zhang, Yunhai

AU - Wan, Feng

AU - Wang, Chi

AU - Gan, Yong

N1 - Copyright © 2017. Published by Elsevier B.V.

PY - 2018/1

Y1 - 2018/1

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1016/j.jconrel.2017.11.012

DO - 10.1016/j.jconrel.2017.11.012

M3 - Journal article

C2 - 29129657

VL - 269

SP - 159

EP - 170

JO - Journal of Controlled Release

JF - Journal of Controlled Release

SN - 0168-3659

ER -

ID: 185717905