Macromolecular Research

The Polymer Society of Korea (한국고분자학회)
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Biodistribution and Genotoxicity of Transferrin-Conjugated Liposomes/DNA Complexes in Mice

  • Lee Sang Mi (College of Pharmacy, Sookmyung Women's University) ;
  • Kim Jin-Seok (College of Pharmacy, Sookmyung Women's University) ;
  • Oh Yu-Kyoung (Pocheon CHA University) ;
  • Lee Yong-Bok (College of Pharmacy, Chonnam National University) ;
  • Sah Hongkee (College of Pharmacy, Catholic University of Daegu)
  • Published : 2005.06.01
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Abstract

Transferrin-conjugated liposomes ($T_f$-liposomes) were made and formulated with pCMVluc DNA to form a lipoplex. Among the various formulations studied, the $T_f$-liposome: pCMVluc DNA complex at a ratio of 5: 1 (wt/wt) showed the highest transfection efficiency, which was twice that of $Lipofectin^{TM}$ on HeLa cells. The maxi-mum tolerated dose (MTD) of this lipoplex formulation from a single intravenous injection was over 10 mg/kg in healthy ICR mice. The RT-PCR results showed that the highest level of luciferase mRNA was detected in the lungs, followed by the liver, spleen, heart and kidneys, after an intravenous injection into mice. Two weeks after the injection, the levels of luciferase mRNA decreased gradually in the liver, spleen, heart, and kidney, but not in the lungs. The micro-array study showed that the cancer-related genes, including the bcl 6 gene, were highly up-regulated by the treatment with $T_f$-liposome/ pCMVluc DNA complex on HeLa cells, indicating that there were possible interactions between the host chromosomal DNA and the $T_f$-liposome within the cells. The results obtained from this study are expected to be useful for designing a safe and efficient gene delivery system using transferrin-conjugated liposomes.

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