Intravitreal delivery of oligonucleotides by sterically stabilized liposomes

Invest Ophthalmol Vis Sci. 2002 Jan;43(1):253-9.

Abstract

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.

MeSH terms

  • Animals
  • Choroid / metabolism
  • Choroid / pathology
  • Delayed-Action Preparations
  • Drug Delivery Systems*
  • Injections
  • Liposomes
  • Oligonucleotides / administration & dosage*
  • Oligonucleotides / pharmacokinetics*
  • Poly T / administration & dosage*
  • Poly T / pharmacokinetics*
  • Rabbits
  • Retina / metabolism
  • Retina / pathology
  • Thionucleotides / administration & dosage
  • Vitreous Body / metabolism*
  • Vitreous Body / pathology

Substances

  • Delayed-Action Preparations
  • Liposomes
  • Oligonucleotides
  • Thionucleotides
  • Poly T