Delivery of antisense oligonucleotide to the cornea by iontophoresis.

Détails

ID Serval
serval:BIB_FA692FC8F777
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Delivery of antisense oligonucleotide to the cornea by iontophoresis.
Périodique
Antisense and Nucleic Acid Drug Development
Auteur(s)
Berdugo M., Valamanesh F., Andrieu C., Klein C., Benezra D., Courtois Y., Behar-Cohen F.
ISSN
1087-2906 (Print)
ISSN-L
1087-2906
Statut éditorial
Publié
Date de publication
2003
Peer-reviewed
Oui
Volume
13
Numéro
2
Pages
107-114
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
We wished to evaluate the potential of iontophoresis to promote the delivery of antisense oligonucleotides (ODN) directed at the vascular endothelial growth factor (VEGF)-R2 receptor (KDR/Flk) to the cornea of the rat eye. Fluorescence (CY5)-labeled ODNs in phosphate-buffered saline (PBS) (20 microM) were locally administered to rat eyes, and their fate within the anterior segment was studied. Thirty-four male, 5-week-old Wistar rats were used for all experiments. The rats were divided in four groups. In group I (12 rats, 12 eyes), the ODNs (20 microM) were delivered by iontophoresis (300 microA for 5 minutes) using a specially designed corneal applicator. In group II (12 rats, 12 eyes), the ODNs (20 microM) were delivered using the same applicator, but no electrical current was applied. In group III (6 rats, 6 eyes), a corneal neovascular reaction was induced prior to the application of ODNs (20 microM), and iontophoresis electrical current was delivered as for group I rats. Group IV (4 rats, 4 eyes) received ODN (60 microM) iontophoresis application (300 microA for 5 minutes) and were used for ODN integrity studies. The animals were killed 5 minutes, 90 minutes, and 24 hours after a single ODN application and studied. Topically applied ODNs using the same iontophoresis applicator but without current do not penetrate the cornea and remain confined to the superficial epithelial layer. ODNs delivered with transcorneoscleral iontophoresis penetrate into all corneal layers and are also detected in the iris. In corneas with neovascularization, ODNs were particularly localized within the vascular endothelial cells of the stroma. ODNs extracted from eye tissues 24 hours after iontophoresis remained unaltered. The iontophoresis current did not cause any detectable ocular damage under these conditions. Iontophoresis promotes the delivery of ODNs to the anterior segment of the eye, including all corneal layers. Iontophoresis of ODNs directed at VEGF-R2 may be used for the design of specific antiangiogenic strategy in diseases of the cornea.
Mots-clé
Animals, Cornea/metabolism, Epithelium/metabolism, Gene Transfer Techniques, Iontophoresis/methods, Male, Microscopy, Confocal, Neovascularization, Physiologic, Oligonucleotides/chemistry, Oligonucleotides, Antisense/chemistry, Oligonucleotides, Antisense/therapeutic use, Rats, Rats, Wistar, Time Factors
Pubmed
Web of science
Création de la notice
07/04/2014 16:59
Dernière modification de la notice
20/03/2018 13:25
Données d'usage