Complexation of tauro‐ and glyco‐conjugated bile salts with α‐cyclodextrin and hydroxypropyl‐α‐cyclodextrin studied by affinity capillary electrophoresis and molecular modelling

Holm, René; Schönbeck, Christian; Askjær, Sune; Jensen, Henrik; Westh, Peter; Østergaard, Jesper

doi:10.1002/jssc.201100479

Cited by 19 publications

(13 citation statements)

References 75 publications

(137 reference statements)

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“…For example, α-CD has a high affinity for fatty acids, flavor molecules and other hydrophobic molecules [ 2 – 4 ]. However, α-CD has a low affinity for the steroid structure because the cavity size of α-CD is smaller than the structure [ 3 , 5 ]. α-CD has various effects on stabilization of fatty acids, flavor retention and emulsion formation of triglycerides via the formation of an inclusion complex [ 4 , 6 – 8 ].…”

Section: Introductionmentioning

confidence: 99%

A study on the inhibitory mechanism for cholesterol absorption by α-cyclodextrin administration

Furune¹,

Ikuta²,

Ishida³

et al. 2014

Beilstein J. Org. Chem.

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Summary Background: Micelle formation of cholesterol with lecithin and bile salts is a key process for intestinal absorption of lipids. Some dietary fibers commonly used to reduce the lipid content in the body are thought to inhibit lipid absorption by binding to bile salts and decreasing the lipid solubility. Amongst these, α-cyclodextrin (α-CD) is reportedly one of the most powerful dietary fibers for decreasing blood cholesterol. However, it is difficult to believe that α-CD directly removes cholesterol because it has a very low affinity for cholesterol and its mechanism of action is less well understood than those of other dietary fibers. To identify this mechanism, we investigated the interaction of α-CD with lecithin and bile salts, which are essential components for the dissolution of cholesterol in the small intestine, and the effect of α-CD on micellar solubility of cholesterol. Results: α-CD was added to Fed-State Simulated Intestinal Fluid (FeSSIF), and precipitation of a white solid was observed. Analytical data showed that the precipitate was a lecithin and α-CD complex with a molar ratio of 1:4 or 1:5. The micellar solubility of cholesterol in the mixture of FeSSIF and α-CD was investigated, and found to decrease through lecithin precipitation caused by the addition of α-CD, in a dose-dependent manner. Furthermore, each of several other water-soluble dietary fibers was added to the FeSSIF, and no precipitate was generated. Conclusion: This study suggests that α-CD decreases the micellar solubility of cholesterol in the lumen of the small intestine via the precipitation of lecithin from bile salt micelles by complex formation with α-CD. It further indicates that the lecithin precipitation effect on the bile salt micelles by α-CD addition clearly differs from addition of other water-soluble dietary fibers. The decrease in micellar cholesterol solubility in the FeSSIF was the strongest with α-CD addition.

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Section: Introductionmentioning

confidence: 99%

A study on the inhibitory mechanism for cholesterol absorption by α-cyclodextrin administration

Furune¹,

Ikuta²,

Ishida³

et al. 2014

Beilstein J. Org. Chem.

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“…A target temperature of 25°C was selected to allow for comparison with previous investigations, even though this is not the physiologically relevant temperature, where mobility‐shift ACE was found to be an efficient method for investigation of the interaction between glyco‐ and tauro‐conjugated bile salts and neutral CDs . However, the highly charged nature of SBEβCD makes it analytically more challenging as compared to its neutral counter parts.…”

Section: Resultsmentioning

confidence: 99%

Affinity capillary electrophoresis method for investigation of bile salts complexation with sulfobutyl ether‐β‐cyclodextrin

Østergaard

Jensen

Holm

2012

J of Separation Science

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Sulfobutyl ether-β-cyclodextrin (SBEβCD) is utilized in preformulation and drug formulation as an excipient for solubilization of drugs with poor aqueous solubility. Approximately seven negative charges of SBEβCD play a role with respect to solubilization and complexation, but also have an influence on the ionic strength of the background electrolyte when the cyclodextrin is used in capillary electrophoresis. Mobility-shift affinity capillary methods for investigation of the complexation of taurocholate and taurochenodeoxycholate with the negatively charged cyclodextrin derivative applying constant power and ionic strength conditions as well as constant voltage and varying ionic strength were investigated. A new approach for the correction of background electrolyte ionic strength was developed. Mobility-shift affinity capillary electrophoresis experiments obtained at constant voltage and constant power settings were compared and found to provide binding parameters that were in good agreement upon correction. The complexation of taurochenodeoxycholate with SBEβCD was significantly stronger than the corresponding interaction involving taurocholate. The obtained stability constants for the bile salts were in the same range as those previously reported for the interaction with neutral β-cyclodextrins derivatives, i.e. the positions of the negative charges on SBEβCD and the bile salts within the complex did not lead to significant electrostatic repulsion.

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“…It has been shown that both bile salts and phospholipids can act as guest molecules in CD complexes. [216][217][218] As mentioned earlier in this review, in multicomponent systems, competition between different guest molecules may result in reorganization of complexes and in dynamic systems, such as the intestinal environment, complex composition (and, consequently, CD aggregation) can change over time. As a result, the aggregation behavior and overall performance of the formulation in biorelevant media and in pure water may strongly differ.…”

Section: Challenges and Opportunitiesmentioning

confidence: 86%

Self-Assembly of Cyclodextrins and Their Complexes in Aqueous Solutions

Ryzhakov

Thi

Stappaerts

et al. 2016

Journal of Pharmaceutical Sciences

125

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Cyclodextrins (CDs) are enabling pharmaceutical excipients that can be found in numerous pharmaceutical products worldwide. Because of their favorable toxicologic profiles, CDs are often used in toxicologic and phase I assessments of new drug candidates. However, at relatively high concentrations, CDs can spontaneously self-assemble to form visible microparticles in aqueous mediums and formation of such visible particles may cause product rejections. Formation of subvisible CD aggregates are also known to affect analytical results during product development. How and why these CD aggregates form is largely unknown, and factors contributing to their formation are still not elucidated. The physiochemical properties of CDs are very different from simple amphiphiles and lipophilic molecules that are known to self-assemble and form aggregates in aqueous solutions but very similar to those of linear oligosaccharides. In general, negligible amounts of aggregates are formed in pure CD solutions, but the aggregate formation is greatly enhanced on inclusion complex formation, and the extent of aggregation increases with increasing CD concentration. The diameter of the aggregates formed is frequently less than about 300 nm, but visible aggregates can also be formed under certain conditions.

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Complexation of tauro‐ and glyco‐conjugated bile salts with α‐cyclodextrin and hydroxypropyl‐α‐cyclodextrin studied by affinity capillary electrophoresis and molecular modelling

Cited by 19 publications

References 75 publications

A study on the inhibitory mechanism for cholesterol absorption by α-cyclodextrin administration

A study on the inhibitory mechanism for cholesterol absorption by α-cyclodextrin administration

Affinity capillary electrophoresis method for investigation of bile salts complexation with sulfobutyl ether‐β‐cyclodextrin

Self-Assembly of Cyclodextrins and Their Complexes in Aqueous Solutions

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