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Intravitreal delivery of oligonucleotides by sterically stabilized liposomes
Amélie Bochot1, Elias Fattal, Valérie Boutet
1Laboratoire de Physico-Chimie, Pharmacotechnie, Biopharmacie, Unité Mixte de Recherche Centre National de la Recherche Scientifique 8612, Faculté de Pharmacie, Châtenay-Malabry, France.
Purpose:
The efficacy of sterically stabilized liposomes for delivering a model phosphodiester oligonucleotide intravitreally was investigated in the rabbit.
Methods:
Ocular distribution and clearance from the vitreous humor of a model 16-mer oligothymidylate (pdT16) were evaluated in the rabbit by radioactivity measurements after intravitreal injection of either a solution or liposomes containing the [33P]pdT16 oligonucleotide. The integrity of pdT16 was investigated using a competitive hybridization assay.
Results:
The residual concentration of the [33P]pdT16 oligonucleotide within the ocular tissues was significantly increased after intravitreal administration of the liposomal suspension compared with a simple solution. Administration of liposome-encapsulated pdT16 oligonucleotide resulted in sustained release into the vitreous and the retina-choroid compared with release from the solution and in a reduced distribution to nontarget tissues (sclera, lens). In addition, liposomes protected the phosphodiester oligonucleotide against degradation. This was not observed after administration of the free oligonucleotide.
Conclusions:
The intravitreal injection of a phosphodiester oligonucleotide encapsulated within liposomes is a new way of delivering intact oligonucleotide to the eye in a controlled manner. This offers interesting prospects for the treatment of retinal diseases.