Monolayers bile salts

Mita S, Suzuki H, Akita H, et al. Vectorial transport of unconjugated and conjugated bile salts by monolayers of LLC-PK1 cells doubly transfected with human NTCP and BSEP or with rat Ntcp and Bsep. Am J Physiol Gastrointest Liver Physiol 2006 290 G550-G556. 

Table 3 summarizes different additives that have been proposed (1) as solubility enhancers, (2) to reduce adsorption or (3) to increase the biorelevance (pH, bile salts, sink conditions) in in ly r oabsorption models. The maximal tolerable concentration of each was determined by assessing the flux of a hydrophilic marker, the transepithelial electrical resistance (TEER) and/or the release of enzymes or the enzymatic status of the cell monolayers. 

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]. 

Mukaizawa, F., et al., 2009. Novel oral absorption system containing polyamines and bile salts enhances drug transport via both transcellular and paracellular pathways across Caco-2 cell monolayers. hiL J. Pharm. 367 (1-2), 103-108. http //www.ncbi.nlm.nih.gov/ pubmed/18929635 (accessed 10.01.16.). 

Surface studies of insoluble monolayers of all the common unconjugated bile acids, including the unsubstituted cholanoic acid, have been carried out by a number of workers and thoroughly reviewed [5]. Being insoluble non-swelling amphiphiles with limited aqueous solubility, their surface pressure-area (v-A) isotherms can be measured satisfactorily with a Langmuir-Pockels surface balance on an aqueous subphase containing 3-6 M NaCl to salt out polar functions and at sufficient acidic pH (1-3) to prevent ionization [5,6). 

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