CHITOSAN-g-PEI: A NOVEL COPOLYMER FOR MUCOSAL DNA VACCINE DELIVERY

摘要

We have grafted Polyethylenimine (PEI) ofvarious molecular weights on to the backbone ofChitosan in an effort to improve the inherenttransfection efficiency of Chitosan. We hypothesizethat the efficacy of mucosal DNA vaccination can besignificantly enhanced by combining themucoadhesive properties of Chitosan with thesuperior transfection efficiency of PEI, whilereducing the toxicity associated with a pure PEIbaseddelivery vehicle. Here we present a novelgrafting technique for conjugating PEI on thiolatedChitosan. Efficient thiolation of Chitosan wasdemonstrated by Ellman's assay and qualitativeindication of successful PEI grafting has beenestablished by FT-IR spectroscopy. We also showthat these Chitosan-PEI graft copolymers can beused to form nanocomplexes, by complexcoacervation with negatively charged Carboxy-MethylCellulose (CMC). Particle characterizationstudies indicate that Chitosan-g-PEI nanoparticles (～300 nm in size, measured by dynamic lightscattering) exhibit a significant increase in cationicsurface charge (zeta potential) over non-graftedChitosan particles. Currently we are investigatingand optimizing the conditions for efficient surfaceloading of plasmid DNA (pDNA) andoligonucleotides (ODN) on these cationicnanocomplexes for use in mucosal DNA vaccination.