Reza Kazemi Oskuee - Neurogenic Inflammation Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran | Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
Vahideh Zakeri - School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Leila Gholami - Targeted Drug Delivery Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
Bizhan Malaekeh-Nikouei - Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

Objective(s): Although viral vectors are considered efficient gene transfer agents, their board application has been limited by toxicity, immunogenicity, mutagenicity and small gene carrying capacity. Non-viral vectors are safe but they suffer from low transfection efficiency. In the present study, polyallylamine (PAA) in two molecular weights (15 and 65 kDa) was modified by alkane derivatives in order to increase transfection activity and to decrease cytotoxicity. Materials and Methods: Modified PAA was synthesized using three alkane derivatives (1-bromobutane, 1-bromohexane and 1-bromodecane) in different grafting percentages (10, 30 and 50). The condensation ability of modified PAA was determined by ethidium bromide test. The prepared polyplexes, complexes of modified PAA and DNA, were characterized by size and zeta potential. Transfection activity of polyplexes was checked in Neuro2A cells. The cytotoxicity of vector was examined in the same cell line.Results: DNA condensation ability of PAA was decreased after modification but modified polymer could still condense DNA at moderate and high carrier to plasmid (C/P) ratios. Most of polyplexes composed of modified polymer had mean size less than 350 nm. They showed a positive zeta potential, but some vectors with high percentage of grafting had negative surface charge. Transfection efficiency was increased by modification of PAA by 1-bromodecane in grafting percentages of 30 and 50%. Modification of polymer reduced polymer cytotoxicity especially in C/P ratio of 2. Conclusion: Results of the present study indicated that modification of PAA with alkane derivatives can help to prepare gene carriers with better transfection activity and less cytotoxicity.

Alkane derivatives, Cytotoxicity, Gene delivery, Polyallylamine