A comparison of triton X‐100 and the bile salt taurocholate as micellar ionophores or fusogens in phospholipid vesicular membranes

Hunt, G.R.A.

doi:10.1016/0014-5793(80)81014-3

Cited by 35 publications

(16 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the fact that part of the 31p isotropic signal originates from inverted micelles located inside the brush-border membranes cannot be excluded. It has been demonstrated that in model membrane systems bile salt taurocholate can act as a micellar ionophore for Pr 3+ by a transbilayer movement of inverted micelles {Pr(bile salt)4} [15,16]. Furthermore, the formation of inverted micelles or hexagonal phases is related to the nature of the phospholipids.…”

Section: Discussionmentioning

confidence: 98%

See 1 more Smart Citation

Effect of micellar lipids on rabbit intestinal brush-border membrane phospholipid bilayer integrity studied by31P NMR

et al. 1985

View full text Add to dashboard Cite

The effect of biliary salts and fatty acids on the bilayer structure of rabbit intestinal brush-border membranes was studied using the nonperturbing probe 31P NMR. The broad, asymmetric lineshape of the 31P NMR spectrum of isolated brush-border vesicles demonstrates that their component phospholipids are organized in extended bilayers. These membranes are not significantly perturbed by incubation with physiological concentrations of biliary salts (3, 9, 18 mM), demonstrating that the vesicles are highly stable, corresponding to their biological function. However, the emergence of a narrow peak superimposed on the broad lineshape indicates that a small proportion of the membrane phospholipids has reached isotropic motion, which may correspond to external or internal micellar structures. Incubation with mixed micelles of fatty acids and taurochlorate show that long-chain fatty acids enhance the membrane-perturbing effect of taurocholate while short-chain, water-soluble fatty acids do not, suggesting a difference in the absorption mechanisms.

show abstract

Section: Discussionmentioning

confidence: 98%

“…A part of this work has previously been presented at the 24th International Conference on the Biochemistry of Lipids, September [14][15][16] 1983, Toulouse, France.…”

mentioning

confidence: 98%

Effect of micellar lipids on rabbit intestinal brush-border membrane phospholipid bilayer integrity studied by31P NMR

et al. 1985

View full text Add to dashboard Cite

show abstract

“…In favor of some common mechanism is the fact that soluble amphiphiles have often been involved in cell fusion (Howell & Lucy, 1969;Lucy, 1970) as well as vesicle growth (Hunt, 1980;Kantor & Prestegard, 1975) processes. However, not all cell fusogens were effective in promoting vesicle growth.…”

Section: Discussionmentioning

confidence: 99%

Increase in size of sonicated phospholipid vesicles in the presence of detergents

et al. 1982

View full text Add to dashboard Cite

Triton X-100, sodium dodecylsulphate, sodium cholate, and beta-octylglucoside increase the size of sonicated, but not of unsonicated, phospholipid vesicles above the Tc gel to liquid-crystalline transition temperature. Lysophosphatidylcholine or glyceryl monooleate do not increase liposome size under these circumstances. The observed phenomenon of vesicle growth is virtually unaffected by phospholipid composition, surface potential, calcium ions, EDTA, or albumin. The presence of cholesterol makes the vesicles more susceptible to detergent-induced growth. The presence of detergents, even at concentrations much lower than required to observe any increase in vesicle size, favors the liberation of vesicle contents. These results may have implications concerning membrane fusion as well as the reconstitution of membrane proteins in the presence of detergents.

show abstract

“…While this mode of intramembranous bile salt self-association has been invoked to explain the high solubility of bile salts in membranes and synthetic bilayers (10,19), its functional significance has only recently been addressed. Hunt (43) and Castallino and Violand (44), employing NMR spectroscopy, have suggested that reverse micelles of bile salt molecules account for the rapid transport of lanthanides into unilamellar vesicles, and Hunt (43) suggested, on the basis of kinetic analysis, that transmembrane diffusion of lanthanide/bile salt complexes occurred. However, our study and that of Murakami et al (17) show transport saturation at bile salt concentrations of -12 mM (Fig.…”

Section: Resultsmentioning

confidence: 99%

Nasal absorption of insulin: enhancement by hydrophobic bile salts.

Gordon¹,

Moses²,

Silver³

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

235

View full text Add to dashboard Cite

We demonstrate that therapeutically useful amounts of insulin are absorbed by the nasal mucosa of human beings when administered as a nasal spray with the common bile salts. By employing a series of bile salts with subtle differences in the number, position, and orientation of their nuclear hydroxyl functions and alterations in side chain conjugation, we show that adjuvant potency for nasal insulin absorption correlates positively with increasing hydrophobicity of the bile salts' steroid nucleus. As inferred from studies employing various concentrations of unconjugated deoxycholate and a constant dose of insulin, insulin absorption begins at the aqueous critical micellar concentration of the bile salt and becomes maximal when micelle formation is well established. These and other data are consistent with the complementary hypotheses that bile salts act as absorption adjuvants by (i) producing high juxtamembrane concentrations of insulin monomers via solubilization in mixed bile salt micelles and (ii) forming reverse micelles within nasal membranes, through which insulin monomers can diffuse through polar channels from the nares into the blood stream.Certain small peptides can be absorbed through the nasal mucosa as a "snuff" or directly from aqueous solution (1-5). However, efficacy of absorption is typically low and variable (1-5), and therapeutically important peptides of larger molecular size, such as insulin, are not absorbed to any appreciable degree (6). Within the gastrointestinal tract, bile salts promote the transmembrane movement of endogenous and exogenous lipids (7) and the transmembrane and/or paracellular movement of several small endogenous and exogenous polar molecules-e.g., water (7), inorganic electrolytes (7), polyethylene glycols (8), and oxalate (9). Because of these functions, as well as their detergent-like properties on biomembranes (10), bile salts are potential adjuvants for transmucosal delivery of drugs and have been widely explored for this purpose (11-17). Although there is abundant physical-chemical information concerning the micellar properties of bile salt molecules as well as their interactions with membrane and exogenous lipids (18,19), little is known about the mechanisms by which these molecules might enhance transmucosal absorption of drugs (17). As shown by us and others, bile salts promote the nasal absorption of insulin in man (20, 21) as well as in laboratory animals (6, 22). Nevertheless, previous studies in rats, employing a range of bile salt species, failed to define any useful structure-function relationships (23). We now report structure-function studies on a series of naturally occurring bile salts by testing their ability to enhance insulin absorption across the human nasal mucosa when administered intranasally as an insulin/bile salt spray. Dramatic differences in insulin absorption were observed between closely related bile salt species; the pattern was shown to be determined by the hydrophilic-hydrophobic balance (24) of the hydroxyl-substituted steroi...

show abstract

A comparison of triton X‐100 and the bile salt taurocholate as micellar ionophores or fusogens in phospholipid vesicular membranes

Cited by 35 publications

References 21 publications

Effect of micellar lipids on rabbit intestinal brush-border membrane phospholipid bilayer integrity studied by31P NMR

Effect of micellar lipids on rabbit intestinal brush-border membrane phospholipid bilayer integrity studied by31P NMR

Increase in size of sonicated phospholipid vesicles in the presence of detergents

Nasal absorption of insulin: enhancement by hydrophobic bile salts.

Contact Info

Product

Resources

About