Synthesis and in vitro Property Study of Polyaspartamides

Cationic polyaspartamides including poly-α,β-N＇-（2-aminoethyl）-L-aspartamide] （PAEA）, poly-α,β-N＇-（4- aminobutyl）-L-aspartamide] （PABA）, poly-α,β-N＇-（6-aminohexyl）-L-aspartamide] （PAHA）, poly-α,β-N＇-（5-amino- 3-azapentyl）-L-aspartamide] （PAAPA） and poly-α,β-N＇-（8-amino-3,6-diazaoctyl）-L-aspartamide] （PADAOA） were synthesized from polysuccinimide. Their properties were evaluated by ^1H NMR, IR, GPC, fluorescence measurement and in vitro cytotoxicity assays. The molecular weights per primary amine charge group of PAEA（1） （Mn= 2229）, PAAPA and PADAOA are 212, 279, and 226. Polyaspartamides including PAEA（1）, PAAPA, PADAOA and low molecular weight PAHA are markedly less toxic than poly（ethyleneimine） and poly（L-lysine）, however, PABA and higher molecular weight PAHA are slightly less toxic than poly（L-lysine）. Cell cytotoxicity of PAHA was seen to decrease with increasing molecular weight of PAHA, due to water solubility reduction. The negatively charged plasmid DNA has been found to be completely neutralized and complexed by the cationic polyaspartamides at an N/P ratio of 5 ： 1 to 10 ： 1, forming self-assembled polyplexes via ionic interactions. These polyaspartamide/DNA complexes possess stable zeta potentials and mean particle diameters of about 180 nm for PAEA （1）/DNA and PAAPA/DNA complexes and 280 nm for PADAOA/DNA complexes.

Synthesis and in vitro Property Study of Polyaspartamides

Cationic polyaspartamides including poly-α,β-N′-(2-aminoethy1)-L-aspartamide] (PAEA), poly-α,β-N′-(4-aminobutyl)-L-aspartamide] (PABA), poly-α,β-N′-(6-aminohexyl)-L-aspartamide] (PAHA), poly-α,β-N′-(5-amino-3-azapentyl)-L-aspartamide] (PAAPA) and poly-α,β-N′-(8-amino-3,6-diazaoctyl)-L-aspartamide] (PADAOA) were synthesized from polysuccinimide. Their properties were evaluated by ¹H NMR, IR, GPC, fluorescence measurement and in vitro cytotoxicity assays. The molecular weights per primary amine charge group of PAEA(1) (M_n=2229), PAAPA and PADAOA are 212, 279, and 226. Polyaspartamides including PAEA(1), PAAPA, PADAOA and low molecular weight PAHA are markedly less toxic than poly(ethyleneimine) and poly(L-lysine), however, PABA and higher molecular weight PAHA are slightly less toxic than poly(L-lysine). Cell cytotoxicity of PAHA was seen to decrease with increasing molecular weight of PAHA, due to water solubility reduction. The negatively charged plasmid DNA has been found to be completely neutralized and complexed by the cationic polyaspartamides at an N/P ratio of 5:1 to 10:1, forming self-assembled polyplexes via ionic interactions. These polyaspartamide/DNA complexes possess stable zeta potentials and mean particle diameters of about 180 nm for PAEA (1)/DNA and PAAPA/DNA complexes and 280 nm for PADAOA/DNA complexes.