Untitled

Abstract

The effects of the absorption enhancer sodium caprate on human intestinal epithelial cells were investigated using Caco-2 cell monolayers. The effects on epithelial integrity and drug transport are dependent on time and concentration and are decreased by Ca2+, most likely through the formation of Ca2+ soaps. Morphological data indicate that exposure to sodium caprate results in cytoskeletal changes and in structural alterations of the tight junctions in the form of dilatations, while the effects on the apical cell membranes are limited. We conclude that sodium caprate increases the absorption of drugs mainly by the paracellular route.

Permeation enhancement of octreotide by specific bile salts in rats and human subjects: in vitro, in vivo correlations

“…This finding is in agreement with other studies showing a decrease of transepithelial resistance and an increased mannitol or PEG-flux in the presence of di-and trihydroxylated bile salts (Anderberg et al, 1992). It might also be speculated that insertion of the CDCA into the lipid membrane results in an altered membrane fluidity, thereby influencing the functional integrity of the intercellular tight junctions (Lee et al, 1991).…”

“…It is more likely that the bile salts exerted their effects by the formation of mixed micelles and by their detergent-like properties as indicated by increased permeation of the paracellular marker PEG-4000 and by the increased release of LDH. The finding, that the release of cytosolic LDH is increased in the presence of increasing doses of CDCA supports previous results showing that mitochondrial dehydrogenase activity is inhibited by increasing bile salt concentrations in the medium (Anderberg et al, 1992). Both results indicate an increased permeability of the cellular membrane.…”

How “Full” is “Full Fusion” during Exocytosis from Dense Core Vesicles? Effect of SDS on “Quantal” Release and Final Fusion Pore Size

“…49,50 This amounts to only increase the life-time of the nanopores 49 which spontaneously and constantly form and close due to thermal disorders in bilipidic membranes. 38 On the one hand, transient stabilization of spontaneously forming nanopores 38 in cell membranes is expected to allow direct calcium ions intake from the extracellular medium 49 without the need of relying on cells exposure to high concentrations pulses of potassium ions. On the other hand, this should also allow the formation of wider exocytotic fusion pores by relaxing at a molecular level the important local curvature strains created into lipid nanotubes or toroid junctions connecting cell and vesicle membranes.…”

“…Presumably, at this concentration, the cell membrane structure is so drastically affected so that significant SDS quantities may diffuse inside the cell to reach vesicles and lyse them allowing a considerable quantity of catecholamine cations to be released and freely diffuse toward the electrode. 49,50 This would lead to broad diffusion-controlled current traces while some intact vesicles may still provide sharp spikes. However, this does not evidence that such spikes featured normal exocytotic processes.…”

“…32 In this work, we wish to contribute to this search by examining the quantitative and kinetic changes induced in PC12 exocytotic events when these are elicited following their brief stimulations by very dilute sodium dodecyl sulfate (SDS) solutions. Based on previous studies, SDS concentrations lower than 400 μM cannot affect cells membranes structure 49,50 but may be transferred across them and weaken actin assembling in sub-membrane cytoskeletons. 49 It is shown hereafter that eliciting release with SDS 350 μM led to physiologically realistic vesicular exocytotic events, i.e., comparable to those elicited by classical methods such as brief stimulations by K + 105 mM, except that the released quantities resulted almost doubled.…”