Autor: |
Debouzy, J.C., Fauvelle, F., Crouzy, S., Girault, L., Chapron, Y., Göschl, M., Gadelle, A. |
Zdroj: |
Journal of Pharmaceutical Sciences; January 1998, Vol. 87 Issue: 1 p59-66, 8p |
Abstrakt: |
□ A nuclear magnetic resonance (NMR) spectroscopy and molecular modeling study of the interaction between α-cyclodextrin (α-CD) and phospholipids with serine, ethanolamine, or choline headgroups is presented. The experimental approach is based on 31P and 1H NMR measurements on small unilamellar vesicles (SUV), multilamellar systems (MLV), and aqueous suspensions of lipids using a direct complex preparation with α-CD. Molecular dynamics computer simulations are used to investigate the trajectory of α-CD in the vicinity of a membrane surface and the influence of the charge and dipole moment of the phospholipid headgroups. These factors of charge and orientation of dipole moment seem to play a key role in the interaction of phospholipids with α-CD and reflect very well the experimentally observed selectivity of the phospholipid –α-CD approach. However, with this approach, there is no evidence for the formation of a complex with the phospholipid headgroup (except for phosphatidylinositol) that results from electrostatic forces. Rather, after a possible extraction of the lipid from the membrane, a classical inclusion of the sn-2chain in the cavity of α-CD occurs. This step depends on the alkyl chain length and saturation state of the lipids as well as on their organization (i.e., as vesicles or dispersions). Based on our results, chemical modifications of the α-CD molecule to control the hemolytic properties of α-CD are discussed. |
Databáze: |
Supplemental Index |
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