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Titolo:
PHARMACOKINETICS IN MICE OF A [H-3] LABELED PHOSPHOROTHIOATE OLIGONUCLEOTIDE FORMULATED IN THE PRESENCE AND ABSENCE OF A CATIONIC LIPID
Autore:
BENNETT CF; ZUCKERMAN JE; KORNBRUST D; SASMOR H; LEEDS JM; CROOKE ST;
Indirizzi:
ISIS PHARMACEUT,2292 FARADAY AVE CARLSBAD CA 92008
Titolo Testata:
Journal of controlled release
fascicolo: 1-2, volume: 41, anno: 1996,
pagine: 121 - 130
SICI:
0168-3659(1996)41:1-2<121:PIMOA[>2.0.ZU;2-U
Fonte:
ISI
Lingua:
ENG
Soggetto:
H-3 LABELED OLIGONUCLEOTIDES; C-ALPHA EXPRESSION; NF-KAPPA-B; ANTISENSE OLIGONUCLEOTIDES; CELLULAR UPTAKE; MODIFIED OLIGODEOXYNUCLEOTIDES; MESSENGER-RNA; CELLS; INHIBITION; BIODISTRIBUTION;
Keywords:
ANTISENSE OLIGONUCLEOTIDE; CATIONIC LIPID; LIPOSOME; PHARMACOKINETICS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
52
Recensione:
Indirizzi per estratti:
Citazione:
C.F. Bennett et al., "PHARMACOKINETICS IN MICE OF A [H-3] LABELED PHOSPHOROTHIOATE OLIGONUCLEOTIDE FORMULATED IN THE PRESENCE AND ABSENCE OF A CATIONIC LIPID", Journal of controlled release, 41(1-2), 1996, pp. 121-130

Abstract

Formulation of phosphorothioate oligonucleotides with cationic lipidsenhances the pharmacological activity of the oligonucleotide in cellular based assay systems. The effect of cationic lipid formulation on the pharmacokinetic behavior of a phosphorothioate oligodeoxynucleotidein mice was investigated in the present study. In the absence of any formulation, the phosphorothioate oligonucleotide exhibited a plasma T-1/2 of 10.2 min and was broadly distributed to many peripheral tissues with liver, kidney, skeletal muscle and skin being the major organs of disposition. Formulating the oligonucleotide with a DMRIE/DOPE (50:50) formulation, such that there was a 2.5:1 positive charge excess onthe lipidic structure, resulted in marked changes in the distributionof the oligonucleotide. Significant increases in the amount of oligonucleotide distributed to liver, lung and spleen were observed when theoligonucleotide was formulated with cationic lipids. These results suggest that it is possible to change the biodistribution of phosphorothioate oligodeoxynucleotides by formulating with cationic liposomes.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 26/09/20 alle ore 07:04:08