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

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

Fingerprint

Chitosan
Liver
Nanoparticles
DNA
Genes
Luciferases
Polyetherimides
Portal Vein
Tail
Rats
Veins
Common Bile Duct
Biliary Tract
Transgenes
Ducts
Transfection
Toxicity
Wistar Rats
Spleen
Kidney

Keywords

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

ASJC Scopus subject areas

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

Cite this

Chitosan-DNA nanoparticles delivered by intrabiliary infusion enhance liver-targeted gene delivery. / Dai, Hui; Jiang, Xuan; Tan, Geoffrey C Y; Chen, Yong; Torbenson, Michael; Leong, Kam W.; Mao, Hai Quan.

In: International Journal of Nanomedicine, Vol. 1, No. 4, 2006, p. 507-522.

Research output: Contribution to journalArticle

Dai, Hui ; Jiang, Xuan ; Tan, Geoffrey C Y ; Chen, Yong ; Torbenson, Michael ; Leong, Kam W. ; Mao, Hai Quan. / Chitosan-DNA nanoparticles delivered by intrabiliary infusion enhance liver-targeted gene delivery. In: International Journal of Nanomedicine. 2006 ; Vol. 1, No. 4. pp. 507-522.
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