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 language | English (US) |
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Pages (from-to) | 507-522 |
Number of pages | 16 |
Journal | International journal of nanomedicine |
Volume | 1 |
Issue number | 4 |
DOIs | |
State | Published - 2006 |
Externally published | Yes |
Keywords
- Chitosan
- Gene delivery
- Liver-targeted
- Nanoparticles
- Retrograde intrabiliary infusion
ASJC Scopus subject areas
- Biophysics
- Bioengineering
- Biomaterials
- Pharmaceutical Science
- Drug Discovery
- Organic Chemistry