BIODEGRADABLE POLYALKYLCYANOACRYLATE NANOPARTICLES FOR THE DELIVERY OF OLIGONUCLEOTIDES

Citation
E. Fattal et al., BIODEGRADABLE POLYALKYLCYANOACRYLATE NANOPARTICLES FOR THE DELIVERY OF OLIGONUCLEOTIDES, Journal of controlled release, 53(1-3), 1998, pp. 137-143
Citations number
14
Categorie Soggetti
Pharmacology & Pharmacy",Chemistry
ISSN journal
01683659
Volume
53
Issue
1-3
Year of publication
1998
Pages
137 - 143
Database
ISI
SICI code
0168-3659(1998)53:1-3<137:BPNFTD>2.0.ZU;2-7
Abstract
Antisense oligonucleotides with base sequences complementary to a spec ific RNA can, after binding to intracellular mRNA, selectively modulat e the expression of a gene. However, these molecules are poorly stable in biological fluids and are characterized by a low intracellular pen etration. In view of using oligonucleotides as active molecules, the d evelopment of polymeric particulate carriers was considered. Oligonucl eotides were associated with biodegradable polyalkylcyanoacrylate nano particles through the formation of ion pairs between the negatively ch arged oligonucleotides and hydrophobic cations. Oligonucleotides bound to these nanoparticles were found to be protected from nuclease attac k in cell culture media and their cellular uptake was increased as the result of the capture of nanoparticles by an endocytotic/phagocytotic pathway. The in vivo pharmacokinetic profile of oligonucleotides free or associated with nanoparticles has been investigated after intraven ous administration to mice and the stability of these molecules has be en evaluated by original methodology based on the use of polyacrylamid e gel electrophoresis (PAGE) followed by multichannel radioactivity co unting. Stability in vivo in the plasma and in the liver was shown to be improved when the oligonucleotides were adsorbed onto the nanoparti cles. These results obtained both in vitro and in vivo open exciting p erspectives for the specific delivery of oligonucleotides to the liver , thus considering this approach for the treatment of liver diseases ( e.g. liver metastasis or hepatitis). (C) 1998 Elsevier Science B.V.