마우스에서 VEGF 발현 Naked DNA 벡터인 pCK-VEGF의 약동력학 및 조직내 분포

Pharmacokinetics and Biodistribution in Mice of pCK-VEGF Expressing Human Vascular Endothelial Growth Factor

We recently developed a high dfficiency expression vector, pCK, which drives a high level of gane expresion in the skeletal muscles of mice. In this study, we investigated the pharmacokinetics and biodistribution of pCK-VEGF expressing human VEGF165 after intravenous or intramuscular administration. The quantity of pCK-VEGF in the tissues of mice was measured by the PCR method which has a detection limit of approxinately 1 pg of the exogenously added plasmid In the case of intravenous administration, the half life of the pCK-VEGF plasmid in the bloodstream was 1.68 min. After inter-muscular adminstration, the half life of pCK-VEGF plasmid in the bloodstrean was 6.78 min. At 90 min post-administration, 30% of the injected pCK-VEGF was found at the site of injection, where it persisted for up to 8 hours. Less than 1.6% of the injected pCK-VEGF plasmid DNA was detected in highly vascularized tissues such as the lung, kidney, and liver at 90 min post-administration administrated pCK- VEGF presisted for longer periods of time in muscls than in other tissues and that direct intra-muscular injection of pCK-VEGF might be useful for local therapeutic angiogensis.