Electron cryo-microscopy reveals mechanism of action of propranolol on artificial membranes.

Détails

ID Serval
serval:BIB_32867
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Electron cryo-microscopy reveals mechanism of action of propranolol on artificial membranes.
Périodique
Journal of liposome research
Auteur(s)
De Carlo S., Fiaux H., Marca-Martinet C.A.
ISSN
0898-2104
Statut éditorial
Publié
Date de publication
2004
Volume
14
Numéro
1-2
Pages
61-76
Langue
anglais
Notes
Publication types: Journal Article - Publication Status: ppublish
Résumé
The pharmacological activity of several amphiphilic drugs is often related to their ability to interact with biological membranes. Propranolol is an efficient multidrug resistance (MDR) modulator; it is a nonselective beta-blocker and is thought to reduce hypertension by decreasing the cardiac frequency and thus blood pressure. It is used in drug delivery studies in order to treat systemic hypertension. We are interested in the interaction of propranolol with artificial membranes, as liposomes of controllable size are used as biocompatible and protective structures to encapsulate labile molecules, such as proteins, nucleic acids or drugs, for pharmaceutical, cosmetic or chemical applications. We present here a study of the interaction of propranolol, a cationic surfactant, with pure egg phosphatidylcholine (EPC) vesicles. The gradual transition from liposome to micelle of EPC vesicles in the presence of propranolol was monitored by time-resolved electron cryo-microscopy (cryo-EM) under different experimental conditions. The liposome-drug interaction was studied with varying drug/lipid (D/L) ratios and different stages were captured by direct thin-film vitrification. The time-series cryo-EM data clearly illustrate the mechanism of action of propranolol on the liposome structure: the drug disrupts the lipid bilayer by perturbing the local organization of the phospholipids. This is followed by the formation of thread-like micelles, also called worm-like micelles (WLM), and ends with the formation of spherical (globular) micelles. The overall reaction is slow, with the process taking almost two hours to be completed. The effect of a monovalent salt was also investigated by repeating the lipid-surfactant interaction experiments in the presence of KCl as an additive to the lipid/drug suspension. When KCl was added in the presence of propranolol the overall reaction was the same but with slower kinetics, suggesting that this monovalent salt affects the general lipid-to-micelle transition by stabilizing the membrane, presumably by binding to the carbonyl chains of the phosphatidylcholine.
Mots-clé
Cryoelectron Microscopy, Kinetics, Liposomes, Membranes, Artificial, Propranolol, Surface-Active Agents
Pubmed
Web of science
Création de la notice
19/11/2007 12:31
Dernière modification de la notice
20/08/2019 13:18
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