Non-viral gene delivery vectors have shown promising potential to treat a variety of inherited and acquired disorders. Among various non-viral systems, cationic polymers have proved to be the most efficient gene carriers as they have the tendency to condense nucleic acids to nanosized particles and improve their transfer inside the cells. Polyethylenimine has been considered as a ‘gold standard’ in gene delivery applications. However, charge-associated toxicity has limited its clinical efficacy. Here, we have tried to address this concern by partially reducing the cationic charge density on branched polyethylenimines (PEIs, 10 and 25 kDa) and simultaneously converting these polymers into their respective nanoparticles using a commercially available reactive crosslinking reagent, diglycidyl-1,2-cyclohexanedicarboxylate (DCD). Varying the amounts of DCD during crosslinking reaction generated two small series of diglycidyl-1,2-cyclohexanedicarboxylate–PEI (DP10 and DP25) nanoparticles with the size ranging from 125–201 nm and zeta potential from +11–20 mV. Though these nanoparticles showed no difference in the nucleic acid condensing ability from their respective native polymers, a significant decrease in their buffering capacity was observed as determined by the acid–base titration method. Upon further evaluation, pDNA complexes of DP10 and DP25 nanoparticles were found to be non-toxic and exhibited several fold higher transfection efficiency than native polymers and the standard transfection reagent, Lipofectamine. Altogether, these results demonstrate that these nanoparticles can effectively be used for future gene delivery applications.
