Bile acids physicochemical properties

Zhou, K., Xia, W., Zhang, C, and Yu, L. (2006). In vitro binding of bile acids and triglycerides by selected chitosan preparations and their physicochemical properties. LWT Food Sci. Technol. 39,1087-1092. 

Hofmann, A.F., and A. Roda. 1984. Physicochemical properties of bile acids and their relationship to biological properties An overview of the problem. J Lipid Res 25 1477. 

Penetration enhancers have different mechanisms of action depending on their physicochemical properties. Some examples of penetration enhancers and their mechanisms are bile salts (micellization and solubilization of epithelial lipids), fatty acids such as oleic acid (perturbation of intracellular lipids) [25,26], azone (l-dodecylazacycloheptan-2-one) (increasing fluidity of intercellular lipids), and surfactants such as sodium lauryl sulfate (expansion of intracellular spaces). The complete list of enhancers and their mechanism of actions are discussed in detail in Chapter 10. 

In this section, we shall consider the last three items, i.e., the surface and bulk interactions of lipolytic products with bile acids. We shall concentrate on the dispersion of lipolytic products in micellar form by bile acid solutions. This subject is complex and difficult to present clearly because it involves the physical chemistry of surface and bulk properties, which has received relatively little attention from physical chemists. We have termed the events occurring during fat digestion as physicochemical events because the chemical events influence and are influenced by the physical properties of the participating molecules. 

Over the last decades, several academic and industrial research programs have been focused on the development and production of appropriate biocompatible formulations that provide enhanced therapeutic performance. Three different strategies can be discerned that are applied separately or in combination (i) addition of excipients to proteins, such as protease inhibitors, penetration or absorption enhancers like bile salts, fatty acids, cyclodextrins or surfactants " (ii) modification of the physicochemical properties of proteins, e.g. by attachment of lipophilic or hydrophilic moieties or (iii) incorporation of proteins into polymeric or liposomal delivery carriers. " A variety of polymeric vectors has been developed and exploited for this purpose, including biodegradable nanoparticles, nanogels, micelles, polymer bioconjugates and soluble nanocomposites. These polymeric carriers are more extensively described in the following sub-sections. 

Pyka, A. Dolowy, M. Application of structural descriptors for the evaluation of some physicochemical properties of selected bile acids. Acta Pol. Pharm.—Drug Res. 2004, 61, 407 13. 

The purpose of this chapter is to cover the physicochemical properties of cholanic acids and their salts. Some 150 cholanic acids are mentioned in Elsevier s Encyclopedia of Organic Chemistry (27) and about 440 monocar-boxylic, unsubstituted hydroxyl, and carbonyl-substituted bile acids are cataloged by Sobotka (28). Obviously, it would be impossible to deal specifically with each one. Many of these acids are by-products of chemical reactions and are not naturally occurring compounds. Further, meaningful physicochemical data are not available for the great majority of bile acids. 

Therefore, I shall concentrate on only those bile acids that have been reasonably well studied from a physicochemical point of view and which have some relation to physiology and biochemistry of living things. Because the specific physical characteristics of the bile acids and their alkaline metal salts vary considerably with the number of hydroxyl groups present on the steroid nucleus, I will present a fairly detailed description of the physicochemical properties of cholanic acid (no hydroxyl groups), monohydroxy, dihydroxy, and trihydroxy bile acids. Since the triketo bile acid (dehydrocholic acid) has been used widely as a choleretic, its properties will also be discussed. Unfortunately, many interesting bile acids and bile alcohols isolated from a variety of vertebrates (29-32) have not been studied physicochemical ly. However, knowing their molecular structure, many of the properties of these compounds can be deduced by comparison with the known properties of bile acids discussed in this chapter. 

The topic of bile acids has been the subject of a number of general reviews and books (28, 29, 30, 33, 34). Certain reviews have dealt, in part, with physicochemical aspects of the bile salts (35-39) or have mentioned physicochemical properties only briefly (28, 30, 34, 40). A review dealing specifically with the physicochemical properties of bile salts and their relation to physiologic function was published in 1967 (1). This chapter will be limited to a discussion of the physicochemical properties of bile acids and their salts. (For physiologic correlations, see 1, 8, 9, 10, 41, and 197.)... 

BAs are steroid compounds, hydroxyl-derivatives of 5-P-cholan-24-oic acid. BAs are the hnal products of the hepatic biotransformation of cholesterol and they are normally present in the bile as mixed micelles. They have different physicochemical properties according to the number, position, and orientation of their hydroxyl groups, and the type of conjugation with glycine and taurine, which forms the glyco- and tauro-derivatives. These factors influence their solubility, hydrophobicity, and detergent properties [35-37]. 

---