Abstract. PEGylated PEIs are intensely studied non-viral vectors for gene delivery, having high transfection efficiencies. Using all-atom molecular dynamics simulations, the interaction of hyperbranched polyethylenimine polyethylene glycol (HPEI-PEG) with DNA was investigated for different number of PEG chains per HPEI core, and, to this end, a new CHARMM Force Field for PEG was developed. The obtained force field parameters are validated by the good agreement of structural measures, such as the radius of gyration, with experimental evidence.
The reported investigations reveal an upper bound for the PEG fraction in the modelled HPEI-PEG polymers. The addition of PEG reduces cytotoxicity, increases solubility, while still ensuring a high efficiency of forming polyplexes with DNA. Useful correlations between the copolymer structure and polyplex properties are observed, along with insights on the dynamics of the formation of hydrogen bonds between the HPEI core and DNA.

Key words: Polyethylenimine, polyethylene glycol, non-viral vector, all-atom molecular dynamics.