The use of the Caco-2 cell culture model to investigate lipid vehicle effects on lipid metabolism and drug permeation

Abstract

The aim of this thesis was to assess the usefulness of the Caco-2 model for screening lipid vehicle excipient effects on intestinal lipoprotein production and secretion, with emphasis on chylomicron secretion. In addition, the potential of the model to identify lymphotropic formulations and to predict lymphatic drug transport, by monitoring drug association with chylomicrons, was investigated. The Caco-2 model, previously established in the laboratory for studying passive drug absorption was optimised for detection of lipid metabolism, specifically the production and secretion of triglyceride rich lipoproteins (TRL - chylomicrons and VLDL). It was found that cells of a higher passage number (68-84 versus 30-50) were required to produce significant levels of TRL. Cell response to various fatty acid stimuli was consistent with reported in vivo data. Oleic acid proved to be a potent stimulator of chylomicron secretion.