Synthesis and preliminary cellular evaluation of phosphonium chitosan derivatives as novel non-viral vector.

Abstract In this study, N -phosphonium chitosans (NPCSs) with two degrees of substitution were synthesized in a homogeneous system as nonviral gene vectors. Grafted polymer/DNA complexes at various charge ratios were formulated and characterized. Particle sizes of NPCS/DNA complexes were between 110 and 160 nm as determined by dynamic light scattering. Accordingly, scanning electron microscopy photo of NPCS/DNA complexes exhibited a compact morphology. Zeta potentials of these complexes changed as the charge ratio and pH varied. The cytotoxicity assay showed that NPCS polymers were less toxic than branched PEI-25K. Furthermore, gene transfection efficiencies of NPCS/DNA complexes showed that the gene transfection ability of the grafted polymer was much better than chitosan and NPCS with the degree of substitution of 21.5% had comparative gene transfection efficiency to branched PEI-25K. Together, these results suggest that the low toxic NPCS grafted polymers could be used as effective gene delivery vectors.