Degradable gene carriers based on oligomerized polyamines

The focus of this work was to develop potentially biodegradable, polycationic gene carriers possessing high efficiency for gene delivery and being essentially non-toxic. A library of 37 soluble polycations was synthesized by oligomerization of low molecular weight oligoamines with three different crosslinkers, dithiobis-succinimidyl proprionate, dimethyl dithiobis-propionamidate, and hexanediol diacrylate. The types of oligoamine and crosslinker influenced biophysical properties such as DNA binding, hemolytic and endosomolytic membrane activity, transfection efficiency and cytotoxicity of the gene carrier. Degradability of polymers based on reductive cleavage of disulfide bonds or ester hydrolysis was demonstrated. Within the library, oligoethylenimine (800 Da)-based polymers showed the highest gene transfer efficiencies and exceeded the golden standard linear polyethylenimine (22 kDa) in terms of activity/toxicity profile.