Chitosan-DNA nanoparticles delivered by intrabiliary infusion enhance liver-targeted gene delivery.

Published

Journal Article

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. RII 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.

Full Text

Cited Authors

  • Dai, H; Jiang, X; Tan, GCY; Chen, Y; Torbenson, M; Leong, KW; Mao, H-Q

Published Date

  • January 2006

Published In

Volume / Issue

  • 1 / 4

Start / End Page

  • 507 - 522

PubMed ID

  • 17369870

Pubmed Central ID

  • 17369870

Electronic International Standard Serial Number (EISSN)

  • 1178-2013

International Standard Serial Number (ISSN)

  • 1176-9114

Digital Object Identifier (DOI)

  • 10.2147/nano.2006.1.4.507

Language

  • eng