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

摘要

We have grafted Polyethylenimine (PEI) of various molecular weights on to the backbone of Chitosan in an effort to improve the inherent transfection efficiency of Chitosan. We hypothesize that the efficacy of mucosal DNA vaccination can be significantly enhanced by combining the mucoadhesive properties of Chitosan with the superior transfection efficiency of PEI, while reducing the toxicity associated with a pure PEIbased delivery vehicle. Here we present a novel grafting technique for conjugating PEI on thiolated Chitosan. Efficient thiolation of Chitosan was demonstrated by Ellman's assay and qualitative indication of successful PEI grafting has been established by FT-IR spectroscopy. We also show that these Chitosan-PEI graft copolymers can be used to form nanocomplexes, by complex coacervation with negatively charged Carboxy- MethylCellulose (CMC). Particle characterization studies indicate that Chitosan-g-PEI nanoparticles (～ 300 nm in size, measured by dynamic light scattering) exhibit a significant increase in cationic surface charge (zeta potential) over non-grafted Chitosan particles. Currently we are investigating and optimizing the conditions for efficient surface loading of plasmid DNA (pDNA) and oligonucleotides (ODN) on these cationic nanocomplexes for use in mucosal DNA vaccination.