An acute and coincident increase in FABP expression and lymphatic lipid and drug transport occurs during intestinal infusion of lipid-based drug formulations to rats

Pharm Res. 2006 Aug;23(8):1786-96. doi: 10.1007/s11095-006-9021-6.

Abstract

Purpose: To determine a) whether administration of lipid-based formulations can acutely up-regulate the intestinal expression of I-FABP and L-FABP and b) whether this occurs coincidentally with an increase in intestinal lymphatic lipid and drug transport.

Methods: The expression of I-FABP and L-FABP mRNA (using q-PCR) and protein (using immunohistochemistry and Western blotting) in enterocytes was compared with data describing transport of lipid and drug into intestinal lymph following infusion of a set of lipid-based formulations.

Results: Administration of relatively small amounts of oleic acid (5-20 mg/h) over a 5 h period to rats acutely up-regulated the expression, and altered the intracellular distribution of, I-FABP and L-FABP in the enterocytes of the small intestinal epithelia. The increase in expression of I-FABP and L-FABP correlated well with previous data describing the transport of lipid and drug into intestinal lymph following infusion of the same formulations.

Conclusion: The expression and intracellular distribution of I-FABP and L-FABP are acutely influenced by lipid infusion over a time period relevant to feeding or the administration of pharmaceutical lipidic formulations, and these changes occur coincidentally with increased drug transport into the lymphatics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport, Active
  • Blotting, Western
  • Chemistry, Pharmaceutical
  • DNA, Complementary / biosynthesis
  • DNA, Complementary / genetics
  • Enterocytes / drug effects
  • Enterocytes / metabolism
  • Fatty Acid-Binding Proteins / biosynthesis*
  • Fatty Acid-Binding Proteins / genetics
  • Immunohistochemistry
  • Intestinal Mucosa / metabolism
  • Intubation, Gastrointestinal
  • Lipids / chemistry
  • Lymph / physiology*
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • Pharmaceutical Preparations / metabolism*
  • RNA, Messenger / biosynthesis
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • DNA, Complementary
  • Fatty Acid-Binding Proteins
  • Lipids
  • Pharmaceutical Preparations
  • RNA, Messenger