Engineered PEI-piperazinyl nanoparticles as efficient gene delivery vectors: evidence from both in vitro and in vivo studies

A small library of polyethylenimine (PEI) nanoparticles (NPs), wherein PEI was crosslinked with piperazinyl linkers, viz., piperazine-N, N'-dibutyric acid and piperazine-N, N'-dipropanal, yielding piperazine-N,N'-dibutyramide-PEI (PBAP) and piperazine-N, N'-dipropyl-PEI (PPP) nanoparticles, was designed and synthesized. The NPs were in the size range 103-216 nm. DNA complexes of all the NPs had low toxicity and exhibited significant enhancement in transfection efficiency compared to parent PEI and commercial transfection agents. Importantly, the transfection activity of NP/DNA complexes was preserved in the presence of serum. Amongst all the formulations, the PBAP4/DNA complex exhibited the highest transfection efficiency in all the cell lines tested. Also, PBAP4 NPs efficiently protected the complexed DNA against DNase in vitro. Intravenous delivery of PBAP4/DNA complex to male Balb/c mice showed the highest gene expression in spleen cells. The results indicate that PBAP nanoparticles may be used for tissue-specific gene delivery in vivo.