Excipient bile acids

Receptor-mediated transporters are excipients that serve as substrates to exploit specific receptors present on cell membranes. Examples of various receptors that have been explored for permeation enhancement include bile acids (45), vitamin Bi2 (46), amino acids (47), and folic acid (48). Most of the work in receptor-mediated transporters is conducted via the use of prodrugs. For example, a prodrug of acyclovir conjugated to bile acids was seen to have higher permeability as compared to the original drug, because of receptor-mediated transport of the prodrug via bile acid transporters (49). 

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. 

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. 

Mrozek et al. synthesized fourteen acyloxy derivatives of 5(S-cholic acid as novel potential transdermal penetration enhancers and intestinal drug absorption modifiers (Figure 49.6). Nontoxic bile acid/salt derivatives (as amphiphilic compounds) are used widely in drug formulations as excipients and can influence gastrointestinal solubility, absorption, and chemical/enzymatic stability of drugs. Transdermal penetration enhancers are special pharmaceutical excipients that interact with skin components to increase the penetration of drugs into blood circulation after topical application. Structure confirmation of all generated compounds was accomplished by H NMR, NMR, IR, and mass spectrometer (MS) spectroscopy. 

Initial attempts at selecting PEs have identified certain surfactants, such as bile salts and fatty acids, which appear to facilitate oligonucleotide absorption. The advantages of these components are many, in that they are endogenous to foods and body constituents, plus the literature is rich with information about the use and exposure of these two classes of compounds [56]. The precise mechanism of action for these PEs is unknown, but is believed to involve a disruption of the mucus layer barrier, an increase in the fluidity of the mucosal membrane, and potentially an opening of the paracellular tight junctions. The mucolytic effect coupled with the increased membrane fluidity imparted by these excipients appears to allow in-... 

Typical solid lipids used are glycerides and/or fatty acids, and may constitute 30% of the formulation. These are from the same family of lipids found in parenteral nutrition emulsions, such as Intralipid, which have been successfully administered intravenously for several decades. Typical excipients are Dynasan 112, composed of short chain fatty acids, Compritol, lecithin, used as an emulsifier, and surfactants such as polysorbate 80, polaxamer 188, PVP, bile salts such as sodium glycocholate, and Span 85. Water can be replaced with oils or PEG 600 to yield dispersions which can be filled into soft gelatin capsules. 

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. 

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