The influence of cationic lipid type on in-vitro release kinetic profiles of antisense oligonucleotide from cationic nanoemulsions.

Détails

ID Serval
serval:BIB_347BAE80C745
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
The influence of cationic lipid type on in-vitro release kinetic profiles of antisense oligonucleotide from cationic nanoemulsions.
Périodique
European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.v
Auteur(s)
Hagigit T., Nassar T., Behar-Cohen F., Lambert G., Benita S.
ISSN
0939-6411 (Print)
ISSN-L
0939-6411
Statut éditorial
Publié
Date de publication
2008
Peer-reviewed
Oui
Volume
70
Numéro
1
Pages
248-259
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
Novel formulations of cationic nanoemulsions based on three different lipids were developed to strengthen the attraction of the polyanionic oligonucleotide (ODN) macromolecules to the cationic moieties on the oil nanodroplets. These formulations were developed to prolong the release of the ODN from the nanoemulsion under appropriate physiological dilutions as encountered in the eye following topical application. Increasing the concentration of the new cationic lipid exhibiting two cationic amine groups (AOA) in the emulsion from 0.05% to 0.4% did not alter markedly the particle size or zeta potential value of the blank cationic nanoemulsion. The extent of ODN association did not vary significantly when the initial concentration of ODN remained constant at 10 microM irrespective of the cationic lipid nature. However, the zeta potential value dropped consistently with the low concentrations of 0.05% and 0.1% of AOA in the emulsions suggesting that an electrostatic attraction occurred between the cationic lipids and the polyanionic ODN molecules at the o/w interface. Only the nanoemulsion prepared with N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium salts (DOTAP) remained physically stable over time. DOTAP cationic lipid nanoemulsion was the most efficient formulation capable of retaining the ODN despite the high dilution of 1:100 with simulated tear solution (STS). Less than 10% of the ODN was exchanged in contrast to 40-50% with the other cationic nanoemulsions. The in-vitro release kinetic behavior of ODN exchange with physiological anions present in the STS appears to be complex and difficult to characterize using mathematical fitting model equations. Further pharmacokinetic studies are needed to verify our kinetic assumptions and confirm the in-vitro ODN release profile from DOTAP cationic nanoemulsions.
Mots-clé
Amines/chemistry, Cations, Emulsions, Fatty Acids, Monounsaturated/chemistry, Gene Transfer Techniques, Kinetics, Lipids/chemical synthesis, Lipids/chemistry, Models, Chemical, Nanostructures, Oligonucleotides, Antisense/chemistry, Oligonucleotides, Antisense/metabolism, Particle Size, Quaternary Ammonium Compounds/chemistry, Solubility, Water/chemistry
Pubmed
Web of science
Création de la notice
27/08/2013 10:59
Dernière modification de la notice
20/08/2019 14:21
Données d'usage