Systemic administration of TerplexDNA system: pharmacokinetics and gene expression.

Abstract:

PURPOSE:The aim of this study is to extend our previous studies to investigate the TerplexDNA synthetic gene carrier system in pharmacokinetics, biodistribution, and gene expression in major organs after systemic administration. METHODS:The stability of the TerplexDNA system was analyzed in vitro with a serum incubation assay. The TerplexDNA PK/PD studies were conducted by quantitation of Terplex/radiolabeled DNA [CTP alpha-32P] complexes after rat-tail vein injection. The effect of the TerplexDNA system on gene expression in mouse major organs was analyzed by measuring luciferase activities after systemic administration. RESULTS:The TerplexDNA gene carrier showed significantly longer retention in the vascular space than naked plasmid DNA alone. At early time points (1 h postvenous injection), the lung was the major organ of the TerplexDNA distribution, followed by the liver as a major distribution organ at later time points (24 h postinjection). The major organs of transgene expression after intravenous injection were the liver and heart. CONCLUSION:The TerplexDNA system has the potential for in vivo applications due to its higher bioavailability of plasmid DNA in the tissues, and due to its organ specific distribution.

journal_name

Pharm Res

journal_title

Pharmaceutical research

authors

Yu L,Suh H,Koh JJ,Kim SW

doi

10.1023/a:1013081710135

subject

Has Abstract

pub_date

2001-09-01 00:00:00

pages

1277-83

issue

9

eissn

0724-8741

issn

1573-904X

journal_volume

18

pub_type

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