Mechanism of hepatic targeting via oral administration of DSPE–PEG–cholic acid-modified nanoliposomes

Mechanism of hepatic targeting via oral administration of DSPE–PEG–cholic acid-modified nanoliposomes

Ying Li, Chunyan Zhu Department of Drug Delivery Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People’s Republic of China Abstract: In oral administration, gastrointestinal physiological environment,...

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Autores principales: Li Y, Zhu CY
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2017
Materias:
DSPE–PEG–cholic acid
nanoliposomes
hepatic targeting via oral administration
mechanism
FRET
Medicine (General)
R5-920
Acceso en línea:https://doaj.org/article/227e8d53097b4019924d7d993367d86b
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spelling oai:doaj.org-article:227e8d53097b4019924d7d993367d86b2021-12-02T05:39:44ZMechanism of hepatic targeting via oral administration of DSPE–PEG–cholic acid-modified nanoliposomes1178-2013https://doaj.org/article/227e8d53097b4019924d7d993367d86b2017-02-01T00:00:00Zhttps://www.dovepress.com/mechanism-of-hepatic-targeting-via-oral-administration-of-dspendashpeg-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Ying Li, Chunyan Zhu Department of Drug Delivery Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People’s Republic of China Abstract: In oral administration, gastrointestinal physiological environment, gastrointestinal epithelial cell membranes, and blood circulation are typical biological barriers to hepatic delivery of ligand-modified nanoparticle drug delivery systems. To elucidate the mechanism of oral hepatic targeting of cholic acid receptor-mediated nanoliposomes (LPs) (distearoyl phosphatidylethanolamine–polyethylene glycol–cholic acid-modified LPs, CA-LPs), evaluations were performed on colon cancer Caco-2 cell monolayers, liver cancer HepG2 cells, and a rat intestinal perfusion model. CA-LPs, ~100 nm in diameter, exhibited sustained-release behavior and had the greatest stability in rat gastrointestinal fluid and serum for both size and entrapment efficiency. CA-LPs demonstrated highest transport across Caco-2 cells and highest cellular uptake by HepG2 cells. The enhanced endocytosis of CA-LPs was found to be mediated by Na+/taurocholate cotransporting polypeptide and involved the caveolin-mediated endocytosis pathway. Further, we used fluorescence resonance energy transfer (FRET) technology to show that the CA-LPs maintained their structural integrity in part during the transport across the Caco-2 cell monolayer and uptake by HepG2 cells. Keywords: DSPE–PEG–cholic acid, nanoliposomes, hepatic targeting via oral administration, mechanism, FRETLi YZhu CYDove Medical PressarticleDSPE–PEG–cholic acidnanoliposomeshepatic targeting via oral administrationmechanismFRETMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 1673-1684 (2017)
institution DOAJ
collection DOAJ
language EN
topic DSPE–PEG–cholic acid
nanoliposomes
hepatic targeting via oral administration
mechanism
FRET
Medicine (General)
R5-920
spellingShingle DSPE–PEG–cholic acid
nanoliposomes
hepatic targeting via oral administration
mechanism
FRET
Medicine (General)
R5-920
Li Y
Zhu CY
Mechanism of hepatic targeting via oral administration of DSPE–PEG–cholic acid-modified nanoliposomes
description Ying Li, Chunyan Zhu Department of Drug Delivery Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People’s Republic of China Abstract: In oral administration, gastrointestinal physiological environment, gastrointestinal epithelial cell membranes, and blood circulation are typical biological barriers to hepatic delivery of ligand-modified nanoparticle drug delivery systems. To elucidate the mechanism of oral hepatic targeting of cholic acid receptor-mediated nanoliposomes (LPs) (distearoyl phosphatidylethanolamine–polyethylene glycol–cholic acid-modified LPs, CA-LPs), evaluations were performed on colon cancer Caco-2 cell monolayers, liver cancer HepG2 cells, and a rat intestinal perfusion model. CA-LPs, ~100 nm in diameter, exhibited sustained-release behavior and had the greatest stability in rat gastrointestinal fluid and serum for both size and entrapment efficiency. CA-LPs demonstrated highest transport across Caco-2 cells and highest cellular uptake by HepG2 cells. The enhanced endocytosis of CA-LPs was found to be mediated by Na+/taurocholate cotransporting polypeptide and involved the caveolin-mediated endocytosis pathway. Further, we used fluorescence resonance energy transfer (FRET) technology to show that the CA-LPs maintained their structural integrity in part during the transport across the Caco-2 cell monolayer and uptake by HepG2 cells. Keywords: DSPE–PEG–cholic acid, nanoliposomes, hepatic targeting via oral administration, mechanism, FRET
format article
author Li Y
Zhu CY
author_facet Li Y
Zhu CY
author_sort Li Y
title Mechanism of hepatic targeting via oral administration of DSPE–PEG–cholic acid-modified nanoliposomes
title_short Mechanism of hepatic targeting via oral administration of DSPE–PEG–cholic acid-modified nanoliposomes
title_full Mechanism of hepatic targeting via oral administration of DSPE–PEG–cholic acid-modified nanoliposomes
title_fullStr Mechanism of hepatic targeting via oral administration of DSPE–PEG–cholic acid-modified nanoliposomes
title_full_unstemmed Mechanism of hepatic targeting via oral administration of DSPE–PEG–cholic acid-modified nanoliposomes
title_sort mechanism of hepatic targeting via oral administration of dspe–peg–cholic acid-modified nanoliposomes
publisher Dove Medical Press
publishDate 2017
url https://doaj.org/article/227e8d53097b4019924d7d993367d86b
work_keys_str_mv AT liy mechanismofhepatictargetingviaoraladministrationofdspendashpegndashcholicacidmodifiednanoliposomes
AT zhucy mechanismofhepatictargetingviaoraladministrationofdspendashpegndashcholicacidmodifiednanoliposomes
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