L Yu1, H Suh, J J Koh, S W Kim. 1. Center for Controlled Chemical Delivery, Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City 84112, USA.
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.
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.
Authors: Zinnia P Parra-Guillén; Gloria González-Aseguinolaza; Pedro Berraondo; Iñaki F Trocóniz Journal: Pharm Res Date: 2010-04-13 Impact factor: 4.200