Back to Search
Start Over
Characterization of a Synthetic Anionic Vector for Oligonucleotide Delivery Using in Vivo Whole Body Dynamic Imaging.
- Source :
- Pharmaceutical Research; Apr2002, Vol. 19 Issue 4, p367-376, 10p
- Publication Year :
- 2002
-
Abstract
- 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<subscript>1/2</subscript>β 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 07248741
- Volume :
- 19
- Issue :
- 4
- Database :
- Complementary Index
- Journal :
- Pharmaceutical Research
- Publication Type :
- Academic Journal
- Accession number :
- 51573817
- Full Text :
- https://doi.org/10.1023/A:1015133205457