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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

Serum ALT, AST, and ALP levels in rats that received nanoparticles and naked DNA through RII (n = 3).Abbreviation: ALT, alanine transaminase; AST, aspartate transaminase; ALP, alkaline phosphatase; PEI, polyethylenimine.
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f8-ijn-1-507: Serum ALT, AST, and ALP levels in rats that received nanoparticles and naked DNA through RII (n = 3).Abbreviation: ALT, alanine transaminase; AST, aspartate transaminase; ALP, alkaline phosphatase; PEI, polyethylenimine.

Mentions: The acute liver damage and toxicity following RII of nanoparticles and naked DNA were assessed by analyzing serum aspartate transaminase (AST) and alanine transaminase (ALT) levels during the experimental period, in comparison with the infusions of PEI-DNA nanoparticles (Figure 8). A slight increase in serum AST and ALT activities was observed 1 day after the administration of naked DNA, followed by a rapid decrease to the normal level by day 3. Chitosan-DNA nanoparticles mediated only a moderate increase of both ALT and AST activities, slightly higher than that of naked DNA group. In contrast, significant elevation of both AST and ALT in the PEI-DNA nanoparticle group was observed (∼1150 IU/L for ALT and ∼900 IU/L for AST). The levels of alkaline phosphatases (ALP) were monitored to reflect potential damage to biliary tree. The ALP levels followed the same trends for all three groups (Figure 8). The transient increase of ALP level indicated that mild damage to biliary tree occurred in response to the infusion pressure, but this damage was transient. Nanoparticle infusions caused higher levels of ALP during the first two days. Throughout the experimental period, bilirubin levels for all groups were in the normal range (5–30 IU/L), indicating that there was no obstructive jaundice caused by the injection procedure (data not shown).


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)

Serum ALT, AST, and ALP levels in rats that received nanoparticles and naked DNA through RII (n = 3).Abbreviation: ALT, alanine transaminase; AST, aspartate transaminase; ALP, alkaline phosphatase; PEI, polyethylenimine.
© Copyright Policy
Related In: Results  -  Collection

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

f8-ijn-1-507: Serum ALT, AST, and ALP levels in rats that received nanoparticles and naked DNA through RII (n = 3).Abbreviation: ALT, alanine transaminase; AST, aspartate transaminase; ALP, alkaline phosphatase; PEI, polyethylenimine.
Mentions: The acute liver damage and toxicity following RII of nanoparticles and naked DNA were assessed by analyzing serum aspartate transaminase (AST) and alanine transaminase (ALT) levels during the experimental period, in comparison with the infusions of PEI-DNA nanoparticles (Figure 8). A slight increase in serum AST and ALT activities was observed 1 day after the administration of naked DNA, followed by a rapid decrease to the normal level by day 3. Chitosan-DNA nanoparticles mediated only a moderate increase of both ALT and AST activities, slightly higher than that of naked DNA group. In contrast, significant elevation of both AST and ALT in the PEI-DNA nanoparticle group was observed (∼1150 IU/L for ALT and ∼900 IU/L for AST). The levels of alkaline phosphatases (ALP) were monitored to reflect potential damage to biliary tree. The ALP levels followed the same trends for all three groups (Figure 8). The transient increase of ALP level indicated that mild damage to biliary tree occurred in response to the infusion pressure, but this damage was transient. Nanoparticle infusions caused higher levels of ALP during the first two days. Throughout the experimental period, bilirubin levels for all groups were in the normal range (5–30 IU/L), indicating that there was no obstructive jaundice caused by the injection procedure (data not shown).

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