The Role of Formamidine Groups in Dextran Based Nonviral Vectors for Gene Delivery on Their Physicochemical and Biological Characteristics.

Dextran-formamidine esters (dextran-N-[(dimethylamino)methylene]-β-alanine ester) with different degrees of substitution (0.45-0.92) are synthesized in an one-pot reaction. Dextran (Mw 60 000 g mol-1 ) is allowed to react with unprotected beta-alanine and iminium chloride and investigated regarding the potential as gene delivery system for the transfer of plasmid DNA. With degrees of substitution ≥ 0.63 improved DNA binding with formation of enzymatically stable complexes of about 130-160 nm with negative surface charges are obtained. These physicochemical characteristics correlated with increasing transfection rates in CHO-K1 cells determined by a luciferase reporter gene assay in dependency of the number of formamidine residues, N/P ratios and amount of DNA. The role of the number of formamidine groups is also highlighted by in vitro cyto- and hemotoxicity tests under the chosen conditions. These results indicate that dextran-formamidine esters are a very promising material for the safe and efficient gene delivery.