- Dai, H. and Jiang, X. and Tan, G. C. and Chen, Y. and Torbenson, M. and Leong, K. W. and Mao, H. Q., Chitosan-DNA nanoparticles delivered by intrabiliary infusion enhance liver-targeted gene delivery,
International Journal of Nanomedicine, vol. 1 no. 4
pp. 507-522 .
(last updated on 2010/06/11)
The goal of this study was to examine the efficacy of liver-targeted gene delivery by chitosan-DNA nanoparticles through retrograde intrabiliary infusion (RII). The transfection efficiency of chitosan-DNA nanoparticles, as compared with PEI-DNA nanoparticles or naked DNA, was evaluated in Wistar rats by infusion into the common bile duct, portal vein, or tail vein. Chitosan-DNA nanoparticles administrated through the portal vein or tail vein did not produce detectable luciferase expression. In contrast, rats that received chitosan-DNA nanoparticles showed more than 500 times higher luciferase expression in the liver 3 days after RII; and transgene expression levels decreased gradually over 14 days. Luciferase expression in the kidney, lung, spleen, and heart was negligible compared with that in the liver. R-II of chitosan-DNA nanoparticles did not yield significant toxicity and damage to the liver and biliary tree as evidenced by liver function analysis and histopathological examination. Luciferase expression by RII of PEI-DNA nanoparticles was 17-fold lower than that of chitosan-DNA nanoparticles on day 3, but it increased slightly over time. These results suggest that RII is a promising routine to achieve liver-targeted gene delivery by non-viral nanoparticles; and both gene carrier characteristics and mode of administration significantly influence gene delivery efficiency.
nanoparticles gene delivery liver-targeted chitosan retrograde intrabiliary infusion water-soluble chitosan naked plasmid DNA rat biliary-tract in-vivo bile-duct transfection efficiency cytokine production cationic liposomes nonviral vectors portal-vein