Inhibition of HIV-1 in cell culture by oligonucleotide-loaded nanoparticles.
Pharm Res
; 18(8): 1096-101, 2001 Aug.
Article
em En
| MEDLINE
| ID: mdl-11587479
ABSTRACT
PURPOSE:
To investigate the potential use of polymeric nanoparticles for the delivery of antisense oligonucleotides in HIV-1-infected cell cultures.METHODS:
Phosphorothioate oligonucleotides were encapsulated into poly (D,L-lactic acid) nanoparticles. Two models of infected cells were used to test the ability of nanoparticles to deliver them. HeLa P4-2 CD4+ cells, stably transfected with the beta-galactosidase reporter gene, were first used to evaluate the activity of the oligonucleotides on a single-round infection cycle. The acutely infected lymphoid CEM cells were then used to evaluate the inhibition of the viral production of HIV-1 by the oligonucleotides.RESULTS:
The addition to infected CEM cells of nanoparticles containing gag antisense oligonucleotides in the nanomolar range led to strong inhibition of the viral production in a concentration-dependent manner. Similar results were previously observed in HeLa P4-2 CD4+ cells. Nanoparticle-entrapped random-order gag oligonucleotides had similar effects on reverse transcription. However, the reverse transcriptase activity of infected cells treated with nanomolar concentrations of free antisense and random oligonucleotides was not affected.CONCLUSIONS:
These results suggest that poly (D,L-lactic acid) nanoparticles may have great potential as an efficient delivery system for oligonucleotides in HIV natural target cells, i.e., lymphocytic cells.
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Base de dados:
MEDLINE
Assunto principal:
Oligonucleotídeos
/
HIV-1
/
Inibidores da Transcriptase Reversa
Limite:
Humans
Idioma:
En
Revista:
Pharm Res
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Suíça