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 Academic Article uri icon

abstract

  • 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.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.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.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.

authors

  • Trevaskis, Natalie L
  • Lo, Chun Min
  • Ma, Li Yun
  • Tso, Patrick
  • Irving, Helen R
  • Porter, Christopher JH
  • Charman, William N

publication date

  • August 2006

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