Hydrophobic and hydrophilic modifications of polyethylenimine towards gene delivery applications

Abstract Non‐viral gene delivery has emerged as a promising approach for therapy in cancer treatment. Polyethylenimine (PEI) is a prominent transfecting agent, but due to toxicity and poor hemocompatibility, its usage for in vivo applications is limited. However, modification of PEI with different chemical groups can lead to conjugates with good transfection efficiency and better cytocompatibility. In this study, the efficiency of PEI derivatives, namely, PEI succinate (PEIS), PEI lauryl succinate (PEILS), PEI laurate (PEIL) was analyzed for gene delivery applications. Apart from biophysical characterization such as size, zeta potential, nanoplex stability and buffering capacity, cellular internalization, polymer trafficking and p53 transgene expression in C6 cell lines were also investigated. The results indicate that PEI conjugated with lauryl succinate act as better transfecting agent with high efficiency compared to other derivatives, and such balanced hydrophilic‐hydrophobic modification of PEI can render it to be a cytocompatible and effective nucleic acid delivery system.