Bile salts permeation enhancer

Bile salts used in permeation enhancement studies include the trihydroxy salts sodium cholate, sodium glycocholate, and sodium taurocholate (Figure 10.2) and the dihydroxy salts sodium deoxycholate, sodium glycodeoxycholate, and sodium taurodeoxycholate. Several in vitro permeation studies carried out in isolated animal buccal mucosa and in vivo bioavailability studies conducted in animals and human subjects have proven their potential as effective buccal permeation enhancers. 

The dihydroxy salts have been reported to be more active permeation enhancers than the trihydroxy salts [9,17], probably related to their increased lipophilicity, although interestingly other studies appear to show equal effectiveness between the two types of salts [18]. The permeation enhancing effect of dihydroxy bile salts seems to be more pronounced at or above... 

Trihydroxy bile salts have also been proven to be effective. Enhanced permeation of mannitol in TR 146 cells (a model for oral cavity mucosa) was noticed when the concentration of sodium taurocholate and sodium glycocholate was about 2- to 3-fold higher than their... 

They are believed to enhance the transbuccal permeation by a mechanism that is similar to that of bile salts, namely, extraction of lipids, protein denaturation, inactivation of enzymes, and swelling of tissues [39], Sodium dodecyl sulfate is reported to have a significant absorption enhancing effect but may also produce damage to the mucosa [13]. The effect of sodium... 

Lecithin (phosphatidylcholine) is a phospholipid, which may be isolated from either egg yolk or soybeans. It is commercially available in high purity for medical uses and has been used to enhance the absorption of insulin in vivo [26]. The antibiotic sodium fusidate, a steroid similar in molecular structure to bile salts has also been shown to have permeation enhancing properties for insulin in vitro [41]. 

Steroidal detergents showing permeation-enhancing properties are bile salts, glycosylated bile acid analogues and saponins. 

Transcellular transport Sorption promoters can be used to enhance the transcellular transport in the intestine, including bile salts and fatty acid esters. They tend to fluidize the lipid bilayer and enhance drug permeation across the membrane. 

Mucus also appears to be a barrier to the permeation enhancing effect of polymeric or monomeric absorption enhancers. In the aforementioned TMC studies, the enhancement effect (enhancement ratio = permeation rate of the drug in the presence of polymer vs. permeation rate of the drug alone) was higher in vitro (Caco-2 cells no mucus secretion) than the absorption enhancement in vivo. Meaney and O Driscoll studied the effect of mucus on the permeation properties of a micellar system consisting of sodium taurocholate in a coculture of Caco-2 and Ht29GlucH (mucin-secreting) cells. They found that the effect of bile salts on the permeation of hydrophilic paracellular markers was increased in the cocultures that were pretreated with the mucolytic compound A/-acetylcysteine. 

Morimoto, K. Uehara, Y. Iwanaga, K. Kakemi, M. Ohashi, Y. Tanaka, A. Nakai, Y. Influence of absorption enhancers (bile salts) and the preservative (benzalkonium chloride) on mucociliary function and permeation barrier function in rabbit tracheas. Eur. J. Pharm. Sci. 1998, 6 (3), 225-230. 

Meaney CM, O Driscoll CM. Comparison of the permeation enhancement potential of simple bile salt and mixed bile salt fatty acid micellar systems using the Caco-2 cell culture model. Int J Pharm 2000 207(10) 21-30. 

Transcellular permeation enhancers include surfactants, medium chain fatty acids, nonionic surfactants,38 sodium cholate and other bile salts,39 and many other surfactants. 

Noninvasive delivery of insulin via most mucosal membranes requires the use of chemical enhancement for notable insulin absorption (see Section 3.3 and Table II). However, most permeation enhancers have, in addition to their effect on the mucosal membrane, an often pronounced influence on insulin three-dimensional structures. Thus, sodium salicylate (Touitou et al, 1987) as well as bile salts (Gordon etal, 1985) have been shown to dissociate insulin oligomers into monomers. This effect improves membrane permeability, but it may also reduce the physical stability and increase the susceptibility of insulin to enzymatic degradation. The exposure of new epitopes may also influence the immunological properties of the insulin formulation. 

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