Light-Scattering Studies on Bile Acid Salts I: Pattern of Self-Association of Sodium Cholate, Sodium Glycocholate, and Sodium Taurocholate in Aqueous Electrolyte Solutions

Chang, Yunik; Cardinal, John R.

doi:10.1002/jps.2600670214

Cited by 30 publications

(9 citation statements)

References 21 publications

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“…This value is slightly higher than the NaTC CMC value obtained in D2O reported by previous work using NMR, [47]but within the similar range of the the CMC values measured by other methods. [34,35,42] Experiments performed in two deuterated buffers Another important factor that can influence bile salt aggregation is the ionic strength of the medium. Ionic strength increase leads to a reduction of the electrostatic repulsion between charged groups.…”

Section: Resultsmentioning

confidence: 99%

Probing the molecular interactions between pharmaceutical polymeric carriers and bile salts in simulated gastrointestinal fluids using NMR spectroscopy

Pigliacelli

Belton

Wilde

et al. 2019

Journal of Colloid and Interface Science

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The number of poorly soluble new drugs is increasing and one of the effective ways to deliver such pharmaceutically active molecules is using hydrophilic polymers to form a solid dispersion. Bile salts play an important role in the solubilisation of poorly soluble compounds in the gut prior to absorption. When a poorly water-soluble drug is delivered using a hydrophilic polymer based solid dispersion oral formulation, it is still unclear whether there are any polymer-bile salt interactions, which may influence the drug dissolution and solubilisation. This study, using two widely used hydrophilic model polymers, Hydroxypropyl methylcellulose (HPMC) and polyvynilpirrolidone (PVP), and sodium taurocholate (NaTC) as the model bile salt, aims to investigate the interactions between the polymers and bile salts in simulated fed state (FeSSIF) and fasted state (FaSSIF) gut fluids. The nature of the interactions was characterised using a range of NMR techniques. The results revealed that the aggregation behaviour of NaTC in FaSSIF and FeSSIF is much more complex than in water. The addition of hydrophilic polymers led to the occurrences of NaTC-HPMC and NaTC-PVP aggregation. For both systems, pH and ionic strength strongly influenced the aggregation behavior, while the ion type played a less significant role. The outcome of this study enriched the understanding of the aggregation behaviour of bile salts and typical hydrophilic pharmaceutical polymers in bio-relevant media. Due to the highly surfaceactive behaviour of the bile salts, such aggregation behaviour is expected to play a role in drug solubilisation in the gut when the drug is delivered by hydrophilic polymer based dispersions.

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Section: Resultsmentioning

confidence: 99%

Probing the molecular interactions between pharmaceutical polymeric carriers and bile salts in simulated gastrointestinal fluids using NMR spectroscopy

Pigliacelli

Belton

Wilde

et al. 2019

Journal of Colloid and Interface Science

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“…), others involve pairs (or higher order complexes) of molecules such as bile acids and α‐tocopherol (Strauch et al . ; Chang & Cardinal, ; Rossi et al . ).…”

Section: Resultsmentioning

confidence: 99%

“…Cholesterol and several related steroids self‐associate under some conditions (Strauch et al . ; Haberland & Reynolds, ; Chang & Cardinal, ). To test for the possibility that ouabain–digoxin antagonism might be due to the association of ouabain with digoxin (thereby reducing the effective concentrations of both agents), we measured the binding of ouabain to digoxin with MS and SPR technologies.…”

Section: Methodsmentioning

confidence: 99%

Ouabain–digoxin antagonism in rat arteries and neurones

Song

Karashima

Hamlyn

et al. 2014

The Journal of Physiology

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Key pointsr 'Classic' cardiotonic steroids (CTSs) all inhibit Na + ,K + -ATPase (Na + pumps) and exert cardiotonic and vasotonic effects. Nevertheless, prolonged ouabain, but not digoxin, administration induces hypertension; moreover, digoxin antagonizes the hypertensinogenic effect of ouabain.r To examine acute ouabain-digoxin interactions, we tested these and related CTSs on myogenic tone (MT) in pressurized rat mesenteric small arteries and glutamate-evoked Ca 2+ transients in primary cultured rat hippocampal neurones.r The CTSs (0.3-10 nM) all augmented MT at 70 mmHg and Ca 2+ signals, but separated into two functional groups according to whether they were ouabain-or digoxin-like. CTSs within each group were synergistic, but between groups, were antagonistic to one another in both assays.r Na + pump αβ protomers may function as tetraprotomers ((αβ) 4 ) with quarter-site reactivity; simultaneous ouabain-and digoxin-like molecule binding promotes tetraprotomer disaggregation, enabling partial protomer reactivation.r These results may reveal why some patients respond poorly to digoxin therapy, and why Na + pumps may be a novel target for therapeutic development.Abstract 'Classic' cardiotonic steroids (CTSs) such as digoxin and ouabain selectively inhibit Na + ,K + -ATPase (the Na + pump) and, via Na + /Ca 2+ exchange (NCX), exert cardiotonic and vasotonic effects. CTS action is more complex than previously thought: prolonged subcutaneous administration of ouabain, but not digoxin, induces hypertension, and digoxin antagonizes ouabain's hypertensinogenic effect. We studied the acute interactions between CTSs in two indirect assays of Na + pump function: myogenic tone (MT) in isolated, pressurized rat mesenteric small arteries, and Ca 2+ signalling in primary cultured rat hippocampal neurones. The 'classic' CTSs (0.3-10 nM) behaved as 'agonists': all increased MT 70 (MT at 70 mmHg) and augmented glutamate-evoked Ca 2+ (Fura-2) signals. We then tested one CTS in the presence of another. Most CTSs could be divided into ouabain-like (ouabagenin, dihydroouabain (DHO), strophanthidin) or digoxin-like CTS (digoxigenin, digitoxin, bufalin). Within each group, the CTSs were synergistic, but ouabain-like and digoxin-like CTSs antagonized one another in both assays: For example, the ouabain-evoked (3 nM) increases in MT 70 and neuronal Ca 2+ signals were both greatly attenuated by the addition of 10 nM digoxin or 10 nM bufalin, and vice versa. Rostafuroxin (PST2238), a digoxigenin derivative that displaces 3 H-ouabain from Na + ,K + -ATPase, and attenuates some forms of hypertension, antagonized the effects of ouabain, but not digoxin. SEA0400, a Na + /Ca 2+ exchanger (NCX) blocker, antagonized the effects of both ouabain and digoxin. CTSs bind to the α subunit of pump αβ protomers. Analysis of potential models suggests that, in vivo, Na + pumps function as tetraprotomers ( (αβ) of a single CTS to one protomer blocks all pumping activity. The paradoxical ability of digoxin-like CTSs to reactivate the ouabain-inhibited com...

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“…QLS measurements have determined the mean hydrodynamic radius ( ) and the polydispersity ( V ) of simple micelles in a TC system as well as mixed micelles in a TC−L system. , In addition, when the molecular weight of simple BS micelles was estimated by measurements of scattered intensity with increasing concentrations (g/dL) of simple BS micelles according to Flory's model, the second virial coefficient represented an interaction between simple BS micelles . However, the values of the molecular weights and second virial coefficient were dependent on the model of micellar formation …”

Section: Introductionmentioning

confidence: 99%

Interactions and Molecular Weights of Simple Micelles and Mixed Micelles in Taurocholate and Taurocholate−Lecithin Solutions

Liu

1997

J. Phys. Chem. B

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A quasielastic light-scattering (QLS) technique was employed to investigate simple micelles and mixed micelles formed in taurocholate (TC) and TC-lecithin (L) solutions. When the size and polydispersity of simple TC micelles were nearly unchanged with total TC concentrations, the simple TC micelles were suggested to be all of a single size. According to the relationship between the total TC concentration and the TC monomer concentration, a monomer-micelle model predicted the aggregation number (n) and the critical micellar concentration (cmc) of simple TC micelles to be 5 and 10 mM. Based on Flory's theory, the scattered intensity, the TC monomer concentration, the molecular weights of simple TC micelles, and mixed TC-L micelles were estimated to be 2138 Da and 35 840 Da. Moreover, the interaction coefficients of simple TC micelles and mixed TC-L micelles were found to be 1.30 × 10 -5 dL mol g -2 and 5.09 × 10 -6 dL mol g -2 . According to Flory's equation, the estimated interaction coefficients and the concentrations of simple TC micelles and mixed TC-L micelles resulted in different values of the proportionality constant. When the proportionality constant values were assumed to be unchanged, significant errors in the determined molecular weights of simple TC micelles and mixed TC-L micelles occurred.

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Light-Scattering Studies on Bile Acid Salts I: Pattern of Self-Association of Sodium Cholate, Sodium Glycocholate, and Sodium Taurocholate in Aqueous Electrolyte Solutions

Cited by 30 publications

References 21 publications

Probing the molecular interactions between pharmaceutical polymeric carriers and bile salts in simulated gastrointestinal fluids using NMR spectroscopy

Probing the molecular interactions between pharmaceutical polymeric carriers and bile salts in simulated gastrointestinal fluids using NMR spectroscopy

Ouabain–digoxin antagonism in rat arteries and neurones

Interactions and Molecular Weights of Simple Micelles and Mixed Micelles in Taurocholate and Taurocholate−Lecithin Solutions

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