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.
OBJECTIVE
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.


CONCLUSIONS
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.
Trevaskis
Natalie L
NL
Department of Pharmaceutics, Victorian College of Pharmacy, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia.
Lo
Chun Min
CM
Ma
Li Yun
LY
Tso
Patrick
P
Irving
Helen R
HR
Porter
Christopher J H
CJ
Charman
William N
WN
D000818:Animals; D001693:Biological Transport, Active; D015153:Blotting, Western; D002626:Chemistry, Pharmaceutical; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D020895:Enterocytes / Q000187:drug effects / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism; D007441:Intubation, Gastrointestinal; D008055:Lipids / Q000737:chemistry; D008196:Lymph / Q000502:physiology*; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018076:DNA, Complementary; D050556:Fatty Acid-Binding Proteins; D008055:Lipids; D004364:Pharmaceutical Preparations; D012333:RNA, Messenger