Zahra Salmasi - Pharmaceutical Research Center, School Of Pharmacy, Mashhad University Of Medical Sciences
Khalil Abnous - Pharmaceutical Research Center, School Of Pharmacy, Mashhad University Of Medical Sciences
Mohammad Ramezani - Pharmaceutical Research Center, School Of Pharmacy, Mashhad University Of Medical Sciences

Gene therapy is emerging as the potential treatment for various forms of cancers. Despite ofconsiderable progress, there are some limitations for clinical use such as providing carriers withhigh transfection efficiency and minimum toxicity. The present study was designed for synthesis ofcarriers with enhancement in gene transfection efficiency and reduction in cytotoxicity. Novelcarriers were synthesized with substitution of 10%, 30% and 50% of Polyethylenimine 25 kDa (PEI25)primary amines with Histidine, 3-Pyridyl acetate and Piperazin. Special characterizations ofcarriers were performed. Particle size and zeta potential of the polyplexes was measured. Ethidiumbromide exclusion assay and buffering capacity of the carriers was evaluated. Transfectionefficiency and cytotoxicity of polymers was measured in murine neuroblastoma cells. Finally, Invivo experiment for determination of polyplexe transfection and biodistribution was performed.The average size of polyplexes was in the range of 81–186 nm and surface charge remained enoughpositive. Carriers with 30% and 50% substitutions of primary amines of PEI 25 with piperazine andhistidine could significantly increase transfection efficiency and decrease cytotoxicity. 24 h afterintravenous administration of the polyplexes in Balb/c mice, high luciferase expression wasdetected in lungs and mortality was decreased compared to PEI25. These modifications of PEI 25 cansignificantly improve transfection efficiency and reduced cytotoxicity. Due to the high geneexpression in lungs with no mortality, this modified carrier could be used for tissue-specific genedelivery in vivo.