@article {17482, title = {Ionically Crosslinked Chitosan Nanoparticles as Gene Delivery Systems: Effect of PEGylation Degree on In Vitro and In Vivo Gene Transfer}, journal = {Journal of Biomedical Nanotechnology}, volume = {5}, year = {2009}, month = {2009-04-01 00:00:00}, pages = {162}, abstract = {

The purpose of this work was to develop a new type of nanoparticles made of PEG-grafted chi-
tosans (CS-g-PEG) using tripolyphosphate (TPP) as a polyanionic crosslinker and to investigate the
potential of these nanostructures as gene carriers. The formation of these nanoparticles was opti-
mised by the evaluation of the combined effects of pH, PEGylation degree and chitosan/crosslinker
ratio on the particle formation. The selected CS-g-PEG/TPP nanoparticles were studied with regard
to their physico-chemical properties, DNA association efficiency as well as to their toxicity and gene
expression in vitro. Furthermore, the best performing nanoparticle prototypes were also evaluated
for their potential for in vivo gene delivery. CS-g-PEG/TPP nanoparticles displayed a high DNA
association efficiency combined with high stability and low cellular toxicity. The results of the in vitro
transfection assays showed positive effects of the PEGylation in the case of particles prepared from
high molecular weight chitosan, while the presence of PEG slightly decreased the efficiency of the
nanoparticles based on low molecular weight chitosan. Overall, high and long lasting gene expres-
sion levels could be observed for all types of nanoparticles. Moreover, CS-g-PEG/TPP nanoparticles
also mediated high gene expression levels in vivo, following nasal administration. These results
indicate the potential of ionically crosslinked CS-g-PEG/TPP nanoparticles as transmucosal gene
delivery systems.

}, keywords = {Chitosan, gene therapy, PEG}, author = {Noemi, C. and Magnus, K. - H. and Novoa-Carballal, R. and Fernandez-Megia, E. and Riguera, R. and Alonso, M.} }