Topical and intravitreous administration of cationic nanoemulsions to deliver antisense oligonucleotides directed towards VEGF KDR receptors to the eye.

Details

Serval ID
serval:BIB_C7DC4D3A6FEB
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Topical and intravitreous administration of cationic nanoemulsions to deliver antisense oligonucleotides directed towards VEGF KDR receptors to the eye.
Journal
Journal of Controlled Release : Official Journal of the Controlled Release Society
Author(s)
Hagigit T., Abdulrazik M., Orucov F., Valamanesh F., Hagedorn M., Lambert M., Lambert G., Behar-Cohen F., Benita S.
ISSN
1873-4995 (Electronic)
ISSN-L
0168-3659
Publication state
Published
Issued date
2010
Peer-reviewed
Oui
Volume
145
Number
3
Pages
297-305
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Abstract
Antisense oligonucleotides (ODNs) specific for VEGFR-2-(17 MER) and inhibiting HUVEC proliferation in-vitro were screened. One efficient sequence was selected and incorporated in different types of nanoemulsions the potential toxicity of which was evaluated on HUVEC and ARPE19 cells. Our results showed that below 10 microl/ml, a 2.5% mid-chain triglycerides cationic DOTAP nanoemulsion was non-toxic on HUVEC and retinal cells. This formulation was therefore chosen for further experiments. In-vitro transfection of FITC ODNs in ARPE cells using DOTAP nanoemulsions showed that nanodroplets do penetrate into the cells. Furthermore, ODNs are released from the nanoemulsion after 48 h and accumulate into the cell nuclei. In both ex-vivo and in-vivo ODN stability experiments in rabbit vitreous, it was noted that the nanoemulsion protected at least partially the ODN from degradation over 72 h. The kinetic results of fluorescent ODN (Hex) distribution in DOTAP nanoemulsion following intravitreal injection in the rat showed that the nanoemulsion penetrates all retinal cells. Pharmacokinetic and ocular tissue distribution of radioactive ODN following intravitreal injection in rabbits showed that the DOTAP nanoemulsion apparently enhanced the intraretinal penetration of the ODNs up to the inner nuclear layer (INL) and might yield potential therapeutic levels of ODN in the retina over 72 h post injection.
Keywords
Administration, Topical, Animals, Cations/chemistry, Cell Line, Cell Line, Tumor, Cell Survival, Emulsions/chemistry, Emulsions/metabolism, Eye/metabolism, Humans, Male, Oligonucleotides, Antisense/administration & dosage, Oligonucleotides, Antisense/genetics, Rabbits, Rats, Rats, Inbred Lew, Thionucleotides/administration & dosage, Vascular Endothelial Growth Factor Receptor-2/genetics
Pubmed
Web of science
Create date
23/08/2013 7:43
Last modification date
20/08/2019 15:43
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