title: Ocular antisense oligonucleotide delivery by cationic nanoemulsion for improved treatment of ocular neovascularization: an in-vivo study in rats and mice.
abstract: The efficacy of an antisense oligonucleotide (ODN17) cationic nanoemulsion directed at VEGF-R2 to reduce neovascularization was evaluated using rat corneal neovascularization and retinopathy of prematurity (ROP) mouse models. Application of saline solution or scrambled ODN17 solution on eyes of rats led to the highest extent of corneal neovascularization. The groups treated with blank nanoemulsion or scrambled ODN17 nanoemulsion showed moderate inhibition in corneal neovascularization with no significant difference with the saline and scrambled ODN17 control solution groups, while the groups treated with ODN17 solution or Avastin® (positive ODN17 control) clearly elicited marked significant inhibition in corneal neovascularization confirming the results reported in the literature. The highest significant corneal neovascularization inhibition efficiency was noted in the groups treated with ODN17 nanoemulsion (topical and subconjunctivally). However, in the ROP mouse model, the ODN17 in PBS induced a 34% inhibition of retinal neovascularization when compared to the aqueous-vehicle-injected eyes. A significantly higher inhibition of vitreal neovascularization (64%) was observed in the group of eyes treated with ODN17 nanoemulsion. No difference in extent of neovascularization was observed between blank nanoemulsion, scrambled ODN17 nanoemulsion, vehicle or non-treated eyes. The overall results indicate that cationic nanoemulsion can be considered a promising potential ocular delivery system and an effective therapeutic tool of high clinical significance in the prevention and forthcoming treatment of ocular neovascular diseases.
authors.affiliation: The Institute for Drug Research, The School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Tal
authors.initials: T
authors.lastname: Hagigit
authors.forename: Muhammad
authors.initials: M
authors.lastname: Abdulrazik
authors.forename: Faty
authors.initials: F
authors.lastname: Valamanesh
authors.forename: Francine
authors.initials: F
authors.lastname: Behar-Cohen
authors.forename: Simon
authors.initials: S
authors.lastname: Benita
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D000818:Animals; D002412:Cations; D016510:Corneal Neovascularization / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry*; D004655:Emulsions; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D049329:Nanostructures / Q000737:chemistry*; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage* / Q000627:therapeutic use; D000644:Quaternary Ammonium Compounds / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012178:Retinopathy of Prematurity / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors; D014822:Vitreous Body / Q000098:blood supply / Q000187:drug effects / Q000473:pathology
chemical_list: D020533:Angiogenesis Inhibitors; D002412:Cations; D004337:Drug Carriers; D004655:Emulsions; D005229:Fatty Acids, Monounsaturated; D016376:Oligonucleotides, Antisense; D000644:Quaternary Ammonium Compounds; D040301:Vascular Endothelial Growth Factor Receptor-2; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane