Influence of the chitosan nature on the transfection efficacy of DNA-loaded nanoparticles after hydrodynamic administration in mice

A commercially available chitosan with a degree of deacetylation (DD) of 85% and a molecular weight (Mw) of 400 kDa was modified by acetylation with acetic anhydride to obtain a chitosan with a DD of 75%. Both polysaccharides were used to prepare DNA-chitosan nanoparticles by charge interactions wit...

Full description

Saved in:
Bibliographic Details
Published in:Journal of microencapsulation 2010-08, Vol.27 (5), p.460-469
Main Authors: Centelles, Miguel N., Isasi, José R., Qian, Cheng, Campanero, Miguel A., Irache, Juan M.
Format: Article
Language:English
Subjects:
Acetylation
Animals
Biological and medical sciences
Chitosan
Chitosan - chemistry
DNA
DNA - administration & dosage
Female
gene delivery
General pharmacology
Genes, Reporter
Green Fluorescent Proteins - genetics
hydrodynamics-based procedure
Luciferases - genetics
Medical sciences
Mice
Mice, Inbred BALB C
nanoparticles
Nanoparticles - chemistry
Nanoparticles - ultrastructure
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Transfection
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:A commercially available chitosan with a degree of deacetylation (DD) of 85% and a molecular weight (Mw) of 400 kDa was modified by acetylation with acetic anhydride to obtain a chitosan with a DD of 75%. Both polysaccharides were used to prepare DNA-chitosan nanoparticles by charge interactions with pDNA (coacervation process). Both resulting nanoparticles showed an almost total DNA loading efficiency (96%) and displayed similar physico-chemical properties with a size of ∼200 nm and a zeta potential close to +20 mV. In order to study the effect of the DD on the properties of DNA-chitosan nanoparticles as gene delivery systems, the hydrodynamics-based procedure was used. The transgene expression was observed using either the green fluorescent protein (GFP) or the luciferase (Luc) as reporter genes. After the hydrodynamic injection, the DNA-chitosan nanoparticles were accumulated in the liver, where the transgene expression was mostly localized. Interestingly, the decrease of the DD affected the transgene expression, improving the initial burst effect and accelerating the DNA release. Both combined effects led to an increase in the transgene expression levels. In addition, the emitted bioluminescence could be detected over 105 days for all the formulations injected. The calculation of the kinetic parameters (Cmax, AUC, Ke, t1/2 Ke and MET) gave some interesting information regarding the abilities to control the DNA release of the two DNA-chitosan formulations tested and allowed narrower comparisons.
ISSN:0265-2048
1464-5246
DOI:10.3109/02652041003638158