Chitosan-DNA nanoparticles delivered by intrabiliary infusion enhance liver-targeted gene delivery.
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.
Dai
Hui
H
Tissue and Therapeutic Engineering Lab, Division of Johns Hopkins in Singapore, Singapore.
Jiang
Xuan
X
Tan
Geoffrey C Y
GC
Chen
Yong
Y
Torbenson
Michael
M
Leong
Kam W
KW
Mao
Hai-Quan
HQ
D000818:Animals; D001652:Bile Ducts; D048271:Chitosan / Q000737:chemistry*; D004247:DNA / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000737:chemistry; D018390:Gene Targeting / Q000379:methods*; D007263:Infusions, Parenteral / Q000379:methods; D008099:Liver / Q000378:metabolism*; D008297:Male; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D014162:Transfection / Q000379:methods*
D004337:Drug Carriers; D004247:DNA; D048271:Chitosan