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Mechanisms of absorption enhancement by medium chain fatty acids in intestinal epithelial Caco-2 cell monolayers.
J Pharmacol Exp Ther. 1995 Nov; 275(2):958-64.JP

Abstract

Sodium salts of medium chain fatty acids (MCFAs) enhance the absorption of hydrophilic drugs across the intestinal mucosa, but the mechanism behind the effect is largely unknown. In this study, the dose-dependent effects of the sodium salts of four MCFAs, C6 (caproate), C8 (caprylate), C10 (caprate) and C12 (laurate), on the permeability of the hydrophilic marker molecule [14C]mannitol were studied in monolayers of the human intestinal epithelial cell line, Caco-2, grown on permeable supports. C8, C10 and C12, but not C6, enhanced the permeability of [14C]mannitol in a dose-dependent manner. Comparison of the cellular effects of the MCFAs at concentrations that gave comparable (8.1- to 8.5-fold) absorption enhancement showed that: 1) C8 was active as absorption enhancer only when the tonicity of the medium was increased; 2) absorption enhancement mediated by C10 was related to a redistribution of the cytoskeleton and structural dilatations in the tight junctions; and 3) C12 was without effect on the cytoskeleton and cellular morphology. Studies on C10 under anisotonic conditions showed that deviations from isotonicity enhanced its effect. These results suggest that structurally similar MCFAs display dramatic differences in their mechanism of action. In addition, the effects of osmolality provide an explanation for the previously reported variability in the efficacy of MCFAs as absorption enhancers.

Authors+Show Affiliations

Department of Pharmacy, Uppsala University, Sweden.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

7473188

Citation

Lindmark, T, et al. "Mechanisms of Absorption Enhancement By Medium Chain Fatty Acids in Intestinal Epithelial Caco-2 Cell Monolayers." The Journal of Pharmacology and Experimental Therapeutics, vol. 275, no. 2, 1995, pp. 958-64.
Lindmark T, Nikkilä T, Artursson P. Mechanisms of absorption enhancement by medium chain fatty acids in intestinal epithelial Caco-2 cell monolayers. J Pharmacol Exp Ther. 1995;275(2):958-64.
Lindmark, T., Nikkilä, T., & Artursson, P. (1995). Mechanisms of absorption enhancement by medium chain fatty acids in intestinal epithelial Caco-2 cell monolayers. The Journal of Pharmacology and Experimental Therapeutics, 275(2), 958-64.
Lindmark T, Nikkilä T, Artursson P. Mechanisms of Absorption Enhancement By Medium Chain Fatty Acids in Intestinal Epithelial Caco-2 Cell Monolayers. J Pharmacol Exp Ther. 1995;275(2):958-64. PubMed PMID: 7473188.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mechanisms of absorption enhancement by medium chain fatty acids in intestinal epithelial Caco-2 cell monolayers. AU - Lindmark,T, AU - Nikkilä,T, AU - Artursson,P, PY - 1995/11/1/pubmed PY - 1995/11/1/medline PY - 1995/11/1/entrez SP - 958 EP - 64 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 275 IS - 2 N2 - Sodium salts of medium chain fatty acids (MCFAs) enhance the absorption of hydrophilic drugs across the intestinal mucosa, but the mechanism behind the effect is largely unknown. In this study, the dose-dependent effects of the sodium salts of four MCFAs, C6 (caproate), C8 (caprylate), C10 (caprate) and C12 (laurate), on the permeability of the hydrophilic marker molecule [14C]mannitol were studied in monolayers of the human intestinal epithelial cell line, Caco-2, grown on permeable supports. C8, C10 and C12, but not C6, enhanced the permeability of [14C]mannitol in a dose-dependent manner. Comparison of the cellular effects of the MCFAs at concentrations that gave comparable (8.1- to 8.5-fold) absorption enhancement showed that: 1) C8 was active as absorption enhancer only when the tonicity of the medium was increased; 2) absorption enhancement mediated by C10 was related to a redistribution of the cytoskeleton and structural dilatations in the tight junctions; and 3) C12 was without effect on the cytoskeleton and cellular morphology. Studies on C10 under anisotonic conditions showed that deviations from isotonicity enhanced its effect. These results suggest that structurally similar MCFAs display dramatic differences in their mechanism of action. In addition, the effects of osmolality provide an explanation for the previously reported variability in the efficacy of MCFAs as absorption enhancers. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/7473188/Mechanisms_of_absorption_enhancement_by_medium_chain_fatty_acids_in_intestinal_epithelial_Caco_2_cell_monolayers_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=7473188 DB - PRIME DP - Unbound Medicine ER -