Dendrosome-based gene delivery

Abstract

Gene transfer to humans requires carriers for the plasmid DNA, which can efficiently and safely carry the gene into the nucleus of the desired cells. The purpose of the present study was to design dendrosomes as a novel, non-viral, vesicular, gene delivery vector and to carry out a comparative study of the relative transfection efficiencies of dendrosomes with standard non-viral, gene delivery vectors. Fourth-generation PAMAM dendrimers were synthesized by double the Michael addition reaction and extensively characterized. The dendrimer–DNA complex was prepared and was confirmed by CD spectroscopy. The dendrosomes were prepared by the reverse phase evaporation method and the entrapment efficiency of the dendrosomal formulation was estimated. In vitro toxicity of the formulation was evaluated by hemolytic toxicity and cytotoxicity studies. Transfection efficiency of the dendrosomal formulations was compared to standard non-viral gene delivery vectors in HEK-293 cell. The results of hemolytic toxicity cytotoxicity studies demonstrated that the dendrosomes possess negligible toxicity as compared to the other formulations and are suitable for in vivo administration. The results of transfection of HEK-293 cell with PGL2 showed that the dendrosomal formulation DF3 possesses superior transfection efficiency against other delivery systems under study. Dendrosomes possess tremendous potential as a novel non-viral and non-toxic gene delivery vector.