Characterization of a synthetic anionic vector for oligonucleotide delivery using in vivo whole body dynamic imaging

Pharm Res. 2002 Apr;19(4):367-76. doi: 10.1023/a:1015133205457.


Purpose: To compare the pharmacokinetics and bioavailability of an oligonucleotide delivered in a free form or using cationic or anionic synthetic carrier systems.

Methods: Whole body dynamic quantitative imaging and metabolism of a HIV antisense oligonucleotide intravenously administered either free or incorporated into synthetic carriers were compared in baboons. using non invasive positron emission tomography and an enzyme-based competitive hybridization assay, respectively.

Results: In its free form, the oligonucleotide showed high liver and kidney concentration, rapid plasmatic degradation and elimination from the body. Use of a cationic vector slightly protected the oligonucleotide against degradation and enhanced uptake by the reticulo-endothelial system. In contrast, the anionic vector dramatically enhanced the uptake in several organs, including the lungs, spleen and brain, with a prolonged accumulation of radioactivity in the brain. Using this vector, intact oligonucleotide was detected in plasma for up to two hours after injection. and the T 1/2beta and distribution volume increased by 4- and 7-fold, respectively. No evidence of toxicity was found after a single dose administration.

Conclusions: The anionic vector improves significantly the bioavailability and the pharmacokinetics of the oligonucleotide, and is a promising delivery system for in vivo administration of therapeutic nucleic acids.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anions / administration & dosage
  • Anions / pharmacokinetics*
  • Drug Carriers / administration & dosage
  • Drug Carriers / pharmacokinetics
  • Drug Delivery Systems / methods*
  • Genetic Vectors / administration & dosage*
  • Genetic Vectors / chemical synthesis*
  • Genetic Vectors / pharmacokinetics
  • Liposomes
  • Male
  • Oligonucleotides, Antisense / administration & dosage
  • Oligonucleotides, Antisense / pharmacokinetics*
  • Papio
  • Tomography, Emission-Computed / methods*
  • Whole-Body Counting / methods


  • Anions
  • Drug Carriers
  • Liposomes
  • Oligonucleotides, Antisense