An Approach to Improve Intestinal Absorption of Poorly Absorbed Water-Insoluble Components <i>via</i> Niemann–Pick C1-Like 1

• Takekawa Yuto

  Faculty of Pharmaceutical Sciences, Hokkaido University

• Sato Yuki

  Faculty of Pharmaceutical Sciences, Hokkaido University

• Yamaki Yoshiaki

  Faculty of Pharmaceutical Sciences, Hokkaido University

• Imai Mei

  Faculty of Pharmaceutical Sciences, Hokkaido University

• Noto Kazuma

  Faculty of Pharmaceutical Sciences, Hokkaido University

• Sumi Masato

  Faculty of Pharmaceutical Sciences, Hokkaido University

• Takekuma Yoh

  Faculty of Pharmaceutical Sciences, Hokkaido University

• Iseki Ken

  Faculty of Pharmaceutical Sciences, Hokkaido University

• Sugawara Mitsuru

  Faculty of Pharmaceutical Sciences, Hokkaido University

Bibliographic Information

Other Title

• An Approach to Improve Intestinal Absorption of Poorly Absorbed Water-Insoluble Components via Niemann-Pick C1-Like 1

Abstract

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 C1-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 µM) 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.

Journal

• Biological and Pharmaceutical Bulletin

  Biological and Pharmaceutical Bulletin 39 (3), 301-307, 2016

  The Pharmaceutical Society of Japan

Keywords

• Niemann–Pick C1-Like 1
• absorption
• cholesterol
• emulsion
• coenzyme Q10

Details

• CRID: 1390282679609576320
• NII Article ID: 130005132319
• NII Book ID: AA10885497
• DOI: 10.1248/bpb.b15-00359
• ISSN: 13475215
• ISSN: 09186158
• HANDLE: 2115/61283
• NDL BIB ID: 027133567
• PubMed: 26934923
• Web Site: http://id.ndl.go.jp/bib/027133567
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I027133567
• Web Site: https://www.jstage.jst.go.jp/article/bpb/39/3/39_b15-00359/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2016310940
• Text Lang: en
• Data Source:
  • JaLC
  • IRDB
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed