Interaction of the Saponin Aescin with Ibuprofen in DMPC Model Membranes

Sreij R, Prevost S, Dargel C, Dattani R, Hertle Y, Wrede O, Hellweg T (2018)
MOLECULAR PHARMACEUTICS 15(10): 4446-4461.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
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Abstract / Bemerkung
In the present work, we study the interaction of the saponin aescin with the nonsteroidal anti-inflammatory drug (NSAID) ibuprofen at concentrations of 1.2-2.5 mM. These amounts are higher than those usually used for medication (10-300 mu M) to show possible structures and formulations for orally absorbed drug delivery systems. It is shown how the interaction of both substances, separately or together, alters the thermotropic phase behavior of the 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) bilayer in the presence of different amounts of aescin, ranging from 20 mu M to 1 mM. The methods of choice are differential scanning calorimetry (DSC), and additionally wide-angle (WAXS) and small angle X-ray scattering (SAXS). We found that these two additives, aescin and ibuprofen, alter the temperature-dependent structural appearance of the DMPC membrane depending on the aescin and drug content. The presence of the saponin and the drug become visible on different length scales, i.e., ranging from a global structural change to inner-membrane interactions. DSC reveals that the drug and saponin alter the cooperativity of the DMPC phase transition in a concentration-dependent manner. Furthermore, there is a significant difference between the drug-containing compared to the drug-free systems. By WAXS, we could resolve that aescin reverses the strong impact of ibuprofen on the diffraction peak of DMPC. Both molecules interact strongly with the phospholipid headgroups. This becomes visible in a changing area per lipid and shifting phase transition to higher temperatures. SAXS experiments reveal that the addition of ibuprofen leads to major morphological changes in the phospholipid bilayer. SAXS experiments performed on representative samples do not only cover the drug saponin interaction within the bilayer from the structural perspective but also confirm the visually observed macroscopic concentration and temperature-dependent phase behavior. Vesicular shape of extruded samples is conserved at low aescin contents. At intermediate aescin content, aggregation between vesicles occurs, whereby the strength of aggregation is reduced by ibuprofen. At high aescin contents, DMPC bilayers are solubilized. The kind of formed structures depends on temperature and drug content. At low temperature, separated bilayer sheets are formed. Their size increases with ibuprofen in a concentration dependent manner. At high temperature, the drug-free system reorganizes into stacked sheets. Whereas sheets at 5 mol % ibuprofen close to vesicles, the ones with 10 mol % of the drug increase massively in size. Altogether, ibuprofen was found to rather enhance than inhibit structural and thermotropic membrane modifications induced by the aescin on the DMPC model membrane.
Stichworte
saponin; ibuprofen; DMPC bilayer; aescin
Erscheinungsjahr
2018
Zeitschriftentitel
MOLECULAR PHARMACEUTICS
Band
15
Ausgabe
10
Seite(n)
4446-4461
ISSN
1543-8384
Page URI
https://pub.uni-bielefeld.de/record/2931988

Zitieren

Sreij R, Prevost S, Dargel C, et al. Interaction of the Saponin Aescin with Ibuprofen in DMPC Model Membranes. MOLECULAR PHARMACEUTICS. 2018;15(10):4446-4461.
Sreij, R., Prevost, S., Dargel, C., Dattani, R., Hertle, Y., Wrede, O., & Hellweg, T. (2018). Interaction of the Saponin Aescin with Ibuprofen in DMPC Model Membranes. MOLECULAR PHARMACEUTICS, 15(10), 4446-4461. doi:10.1021/acs.molpharmaceut.8b00421
Sreij, Ramsia, Prevost, Sylvain, Dargel, Carina, Dattani, Rajeev, Hertle, Yvonne, Wrede, Oliver, and Hellweg, Thomas. 2018. “Interaction of the Saponin Aescin with Ibuprofen in DMPC Model Membranes”. MOLECULAR PHARMACEUTICS 15 (10): 4446-4461.
Sreij, R., Prevost, S., Dargel, C., Dattani, R., Hertle, Y., Wrede, O., and Hellweg, T. (2018). Interaction of the Saponin Aescin with Ibuprofen in DMPC Model Membranes. MOLECULAR PHARMACEUTICS 15, 4446-4461.
Sreij, R., et al., 2018. Interaction of the Saponin Aescin with Ibuprofen in DMPC Model Membranes. MOLECULAR PHARMACEUTICS, 15(10), p 4446-4461.
R. Sreij, et al., “Interaction of the Saponin Aescin with Ibuprofen in DMPC Model Membranes”, MOLECULAR PHARMACEUTICS, vol. 15, 2018, pp. 4446-4461.
Sreij, R., Prevost, S., Dargel, C., Dattani, R., Hertle, Y., Wrede, O., Hellweg, T.: Interaction of the Saponin Aescin with Ibuprofen in DMPC Model Membranes. MOLECULAR PHARMACEUTICS. 15, 4446-4461 (2018).
Sreij, Ramsia, Prevost, Sylvain, Dargel, Carina, Dattani, Rajeev, Hertle, Yvonne, Wrede, Oliver, and Hellweg, Thomas. “Interaction of the Saponin Aescin with Ibuprofen in DMPC Model Membranes”. MOLECULAR PHARMACEUTICS 15.10 (2018): 4446-4461.

1 Zitation in Europe PMC

Daten bereitgestellt von Europe PubMed Central.

Aescin-Cholesterol Complexes in DMPC Model Membranes: A DSC and Temperature-Dependent Scattering Study.
Sreij R, Dargel C, Schweins R, Prévost S, Dattani R, Hellweg T., Sci Rep 9(1), 2019
PMID: 30944386

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