Safety of Liver Surface Instillation of Plasmid DNA in Normal and Carbon Tetrachloride-Induced Hepatitis Mice

Authors

  • Shintaro Fumoto Nagasaki University
  • Hiroyuki Furukawa Nagasaki University
  • Junzo Nakamura Nagasaki University
  • Koyo Nishida Nagasaki University

DOI:

https://doi.org/10.18433/J3SP4H

Abstract

Purpose. We previously demonstrated liver- and lobe-selective gene transfer following instillation of plasmid DNA (pDNA) onto the liver surface in mice. Safety concerns must be resolved prior to future clinical use. Thus, we investigated safety of liver surface instillation of pDNA in normal and hepatitis mice. Methods. pDNA was instilled onto the liver surface in normal and carbon tetrachloride-induced hepatitis mice. Gene expression (luciferase activity) and serum transaminase activities were measured at appropriate time points. Results. Transfection efficiency and target site selectivity were almost the same between the instillation of pDNA using a micropipette and a catheter. Serum transaminase activities 6 h after instillation of pDNA or a vehicle treatment using a micropipette were significantly higher than the no treatment mice, whereas instillation using a catheter did not raise serum transaminase activities throughout the tested time points, suggesting the safety of instillation using a catheter. This safety was also confirmed in hepatitis mice. A dose escalation study verified that liver surface instillation using a catheter did not raise serum transaminase at high doses with saturation of gene expression not only in normal mice, but also in hepatitis mice, supporting the safety of this method. Conclusions. We demonstrated that liver surface instillation of pDNA using a catheter did not raise serum transaminase activities. Information in this study will be useful for future clinical use of liver surface instillation of pDNA using a catheter.

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Published

2011-06-30

How to Cite

Fumoto, S., Furukawa, H., Nakamura, J., & Nishida, K. (2011). Safety of Liver Surface Instillation of Plasmid DNA in Normal and Carbon Tetrachloride-Induced Hepatitis Mice. Journal of Pharmacy & Pharmaceutical Sciences, 14(2), 274–282. https://doi.org/10.18433/J3SP4H

Issue

Section

Pharmaceutical Sciences; Review Articles