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

Dai H, Jiang X, Tan GC, Chen Y, Torbenson M, Leong KW, Mao HQ - Int J Nanomedicine (2006)

Bottom Line: Chitosan-DNA nanoparticles administrated through the portal vein or tail vein did not produce detectable luciferase expression.Luciferase expression in the kidney, lung, spleen, and heart was negligible compared with that in the liver.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.

View Article: PubMed Central - PubMed

Affiliation: Tissue and Therapeutic Engineering Lab, Division of Johns Hopkins in Singapore, Singapore.

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.

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Related in: MedlinePlus

Luciferase expression in major organs of the rats after receiving intrabiliary injection of chitosan-DNA nanoparticles or PEI-DNA nanoparticles containing 200 μg of DNA. Each bar represents mean ± standard deviation (n = 5). Experimental conditions are the same as described in Figure 3.Abbreviation: PEI, polyethylenimine.
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f6-ijn-1-507: Luciferase expression in major organs of the rats after receiving intrabiliary injection of chitosan-DNA nanoparticles or PEI-DNA nanoparticles containing 200 μg of DNA. Each bar represents mean ± standard deviation (n = 5). Experimental conditions are the same as described in Figure 3.Abbreviation: PEI, polyethylenimine.

Mentions: Transgene distribution among different organs was different for gene transfers mediated by chitosan-DNA nanoparticles and PEI-DNA-nanoparticles (Figure 6). This information is important not only in evaluating the liver-targeting effect by the carriers, but also in understanding particle transport mechanism. In rats receiving intrabiliary infusion of chitosan-DNA nanoparticles, transgene expression levels in the kidney, lung, spleen, and heart were negligible (p<0.01). However, in PEI-DNA nanoparticle-transfected rats, low level of luciferase expressions were detected in the lung, spleen, and heart, even though the expression in the liver still accounted for more than 95% of the total transgene expression.


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

Dai H, Jiang X, Tan GC, Chen Y, Torbenson M, Leong KW, Mao HQ - Int J Nanomedicine (2006)

Luciferase expression in major organs of the rats after receiving intrabiliary injection of chitosan-DNA nanoparticles or PEI-DNA nanoparticles containing 200 μg of DNA. Each bar represents mean ± standard deviation (n = 5). Experimental conditions are the same as described in Figure 3.Abbreviation: PEI, polyethylenimine.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1828073&req=5

f6-ijn-1-507: Luciferase expression in major organs of the rats after receiving intrabiliary injection of chitosan-DNA nanoparticles or PEI-DNA nanoparticles containing 200 μg of DNA. Each bar represents mean ± standard deviation (n = 5). Experimental conditions are the same as described in Figure 3.Abbreviation: PEI, polyethylenimine.
Mentions: Transgene distribution among different organs was different for gene transfers mediated by chitosan-DNA nanoparticles and PEI-DNA-nanoparticles (Figure 6). This information is important not only in evaluating the liver-targeting effect by the carriers, but also in understanding particle transport mechanism. In rats receiving intrabiliary infusion of chitosan-DNA nanoparticles, transgene expression levels in the kidney, lung, spleen, and heart were negligible (p<0.01). However, in PEI-DNA nanoparticle-transfected rats, low level of luciferase expressions were detected in the lung, spleen, and heart, even though the expression in the liver still accounted for more than 95% of the total transgene expression.

Bottom Line: Chitosan-DNA nanoparticles administrated through the portal vein or tail vein did not produce detectable luciferase expression.Luciferase expression in the kidney, lung, spleen, and heart was negligible compared with that in the liver.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.

View Article: PubMed Central - PubMed

Affiliation: Tissue and Therapeutic Engineering Lab, Division of Johns Hopkins in Singapore, Singapore.

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.

Show MeSH
Related in: MedlinePlus