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

Hui Dai, Xuan Jiang, Geoffrey C.Y. Tan, Yong Chen, Michael Torbenson, Kam W. Leong, Hai Quan Mao

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)507-522
Number of pages16
JournalInternational journal of nanomedicine
Volume1
Issue number4
DOIs
StatePublished - 2006

Keywords

  • Chitosan
  • Gene delivery
  • Liver-targeted
  • Nanoparticles
  • Retrograde intrabiliary infusion

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Biomaterials
  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry

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