Monolayers bile acids

Anderberg, E.K., C. Nystrom, and P. Artursson. 1992. Epithelial transport of drugs in cell culture. VII Effects of pharmaceutical surfactant excipients and bile acids on transepithelial permeability in monolayers of human intestinal epithelial (Caco-2) cells. J Pharm Sci 81 879. 

We have researched the inclusion abilities of bile acid derivatives by using more than one hundred organic compounds as guest candidates. The inclusion phenomena vary from one case to another, indicating that subtle changes in molecular structures induce alteration in their molecular assemblies. In fact, X-ray diffraction studies prove that the steroidal hosts form various assemblies such as monolayers, bilayers, helical tubes, and so on, as shown in Figure 2. Therefore, systematic investigation of inclusion crystals of bile acid derivatives is expected to reveal a relationship between their molecular structures, assemblies and inclusion behavior. 

The reabsorption of conjugated bile acids is mediated by ASBT, which is localized on the apical membrane of ileal enterocytes in mammals. ASBT is a drug target not only to lower plasma cholesterol level but also to improve intestinal permeability [46]. Although available monolayer cell lines do not express ASBT, it has been expressed in MDCK cells [47]. Human intestine also expresses multiple MCTisoforms [48]. These MCTs are responsible for the absorption of short-chain fatty acid. Expression of MCT in Caco-2 allows it to be an appropriate model to study short-chain fatty acid transport [9, 49, 50]. 

Balakrishnan, A., Sussman, D.J. and Polli, J.E. (2005) Development of stably transfected monolayer overexpressing the human apical sodium-dependent bile acid transporter (hASBT). Pharmaceutical Research, 22, 1269-1280. 

Anderberg EK, Nystrom C, and Artursson P. Epithelial Transport of Drugs in Cell Culture. VII Effects of Pharmaceutical Surfactant Excipients and Bile Acids on Transepithelial Permeability in Monolayers of Human Intestinal Epithelial (Caco-2) Ce ls. JPharm Sci 1992 81 879-887. 

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). 

Sada, K. Sugahara, M. Nakahata. Y. Yasuda. Y. Nishio. A. Miyata, M. First columnar monolayer stracture of bile acids inclusion crystal. Inclusion compounds of 23-nordeoxycholic acid. Chem. Lett. 1998. 31. 

In the small intestine, pancreozymin causes the gallbladder to contract, and bile, a micellar solution of bile acids, lecithin, and cholesterol, is secreted into the duodenum. Pancreozymin also causes discharge and continued synthesis of pancreatic lipase which adsorbs to the oil-water interface, liberating 2-monoglycerides and fatty acids (76). Whether bile acids adsorb to the interface and if so how they spatially orient with respect to lipolytic products and lipase is unknown. At concentrations below the CMC, bile acids will adsorb to monolayers of lipolytic products (77), but no information is available on the interaction of bile acid solutions above their CMC with monolayers of lipolytic products. Somehow, the lipolytic products are transferred to the bulk phase, where they form mixed micelles with bile acid molecules (Fig. 14). 

Amphiphilic molecules contain a polar and an apolar part. As a result, such molecules have an ambiguous (amphi) affinity (philos) for water. The apolar parts behave hydrophobically the water molecules tend to escape from contact with these parts. The polar parts are hydrophilic. They interact favorably with water. The consequence of the amphiphilic character is that the molecules are preferably located at interfaces with water, where the polar parts are exposed to the aqueous phase and the apolar parts to the nonaqueous phase. Low-molecular-weight, amphiphilic compounds are often called surfactants. Well-known examples of surfactants are the classical soaps (single-chain fatty acids), phospholipids, cholesterol, bile acids, lung surfactant, and so on. In Figure 7.1, the chemical structures showing the polar and apolar parts of some of these surfactants are given. Monolayers may also be formed by polymers, polyelectrolytes, and proteins that contain polar and apolar parts. 

Surface studies of insoluble monolayers of various bile acids have been studied by several groups, especially those of Ekwall (102-105) and Otero Aenlle (95, 106-110). In Fig. 12 are given the isotherms of some of the bile acids on 3 Af NaCl, 20°C, compiled from the work of Ekwall et al. (102-105). Figure 13 summarizes the important data derived from these isotherms. A diagrammatic representation of the surface structure of the bile acids at the... 

B. Mixed Monolayers of Bile Acids and Other Amphiphiles... 

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