Model membranes bile salts

Numerous surface-active molecules have been studied as GI absorption promoters in a wide variety of testing conditions, including model membranes, everted intestinal sacs, tissue cultures, intestinal epithelia in diffusion chambers, intact animals, and humans. The physical properties of a chemical enhancer may be strongly dependent on the interactions with the endogenous GI components such as bile salts, pH, and bacteria. Thus the in vitro experiments on enhancing GI absorption are not necessarily predictive of the behavior of the promoter in animals or humans, and we will mainly focus on summarizing results from in vivo studies. 

Several NMR spectroscopic probes have been employed to investigate the interactions of bile salts with model membranes. The results are in general agreement with the deductions above, and suggest additional details ... 

The functional role of bile salts within model and native membranes has begun to be closely scrutinized in recent years [219-223]. This is not surprising in view of the wide use nf bile salts to extract and reconstitute intrinsic membrane proteins [224] and their use in the formation of vesicles without sonication [225]. There is also scientific and clinical interest in the membrane-damaging properties of bile salts [226,227] and toxicity of bile acids used therapeutically [228],... 

The isolated brush border vesicles from the plasma membrane of the microvilU is the simplest in vitro system used so far. The interaction of lipid with rabbit intestinal brush border vesicles has been investigated by Proulx et al. [50] who found that PC, phosphatidylethanolamine, cholesterol, diglyceride as well as fatty acids were taken up by vesicles. Barsukov et al. [51] have shown that transfer of PC from PC vesicles to isolated brush border vesicles can occur in the presence of PC-exchange protein. The use of brush border vesicles is an interesting new approach that permits detailed studies of rate of transfer of specific lipids into the plasma membrane of the enterocyte. The model is seriously hmited by the fact that incubation with solutions containing bile salts at a concentration above the critical micellar concentration will result in partial or total solubilization of the membrane vesicles. 

Immobilized artificial membranes (lAM) are solid membrane mimetics that are covalently bound to the surface of a silica chromatographic support to generate a phospholipid monolayer. lAM chromatography can be applied to measure membrane partitioning of a given compound or to predict bile salt-membrane interactions they may also be used in studies on transcellular absorption. Artificial membranes appear to be well correlated with 1-octanol/water partition coefficients however, since the latter can be well predicted in silico, the real value of AIMs is the ability to study complex molecules or extracts, where in silico prediction is poor. I AM can also be applied to generate large data sets, that in turn can be applied to train and, therefore, improve in silico models by an extensive data input [41]. 

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