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Title
  • en An Approach to Improve Intestinal Absorption of Poorly Absorbed Water-Insoluble Components via Niemann Pick C1-Like 1
Creator
Accessrights open access
Subject
  • Other en Niemann Pick C1-Like 1
  • Other en absorption
  • Other en cholesterol
  • Other en emulsion
  • Other en coenzyme Q10
  • NDC 499
Description
  • Abstract en Dietary and biliary cholesterol absorption contributes to the maintenance of tight control of cholesterol homeostasis. Cholesterol is present as mixed micelles formed by bile salts and phospholipids in the intestinal lumen. Recently, Niemann Pick Cl-Like 1 (NPC1L1) transporter was identified as being critical for cholesterol absorption. However, the uptake mechanism of an enveloped substrate of NPC1L1 in whole lipid emulsion particles remains unclear. In this study, we investigated the uptake mechanism of a substrate of NPC1L1 in lipid emulsion particles. We also investigated whether these particles containing cholesterol can improve the intestinal absorption of other lipophilic components via NPC1L1. The uptake of lysophosphatidylcholine (LPC)-4,4-difluoro-5-(4-phenyl-1,3-butadienyl)-4-bora-3a,4a-diaza-s-indacene-3-propionic acid saccinimidyl ester (BODIPY), a fluorescently labeled phospholipid, in lipid emulsion particles containing cholesterol (1 mu m) was significantly increased compared to that without cholesterol in Caco-2 cells. On the other hand, its increased uptake was significantly inhibited by ezetimibe, a selective inhibitor of NPC1L1. These results suggested that not only cholesterol but also some components in lipid emulsion particles are taken up into enterocytes via NPC1L1. We also examined an approach to improve intestinal absorption of a poorly absorbed water-insoluble component, coenzyme Q10 (CoQ10), by this mechanism. The uptake of CoQ10 in lipid emulsion particles containing cholesterol was significantly increased compared to that without cholesterol. Its increased uptake was significantly inhibited by ezetimibe. Though it is still not clear whether CoQ10 is a substrate of NPC1L1, there is a potential for improvement of the absorption of poorly absorbed components by lipid emulsion particles containing cholesterol.
Publisher en The Pharmaceutical Society of Japan ja 日本薬学会
Date
    Issued2016-03
Language
  • eng
Resource Type journal article
Version Type VoR
Identifier HDL http://hdl.handle.net/2115/61283
Relation
  • isIdenticalTo DOI https://doi.org/10.1248/bpb.b15-00359
  • PMID 26934923
Journal
    • PISSN 0918-6158
      • en Biological & pharmaceutical bulletin
      • Volume Number39 Issue Number3 Page Start301 Page End307
File
Oaidate 2023-07-26