title: A simple approach for producing highly efficient DNA carriers with reduced toxicity based on modified polyallylamine.
abstract: Nowadays gene delivery is a topic in many research studies. Non-viral vectors have many advantages over viral vectors in terms of safety, immunogenicity and gene carrying capacity but they suffer from low transfection efficiency and high toxicity. In this study, polyallylamine (PAA), the cationic polymer, has been modified with hydrophobic branches to increase the transfection efficiency of the polymer. Polyallylamine with molecular weights of 15 and 65kDa was selected and grafted with butyl, hexyl and decyl acrylate at percentages of 10, 30 and 50. The ability of the modified polymer to condense DNA was examined by ethidium bromide test. The complex of modified polymer and DNA (polyplex) was characterized for size, zeta potential, transfection efficiency and cytotoxicity in Neuro2A cell lines. The results of ethidium bromide test showed that grafting of PAA decreased its ability for DNA condensation but vectors could still condense DNA at moderate and high carrier to DNA ratios. Most of polyplexes had particle size between 150 and 250nm. The prepared vectors mainly showed positive zeta potential but carriers composed of PAA with high percentage of grafting had negative zeta potential. The best transfection activity was observed in vectors with hexyl acrylate chain. Grafting of polymer reduced its cytotoxicity especially at percentages of 30 and 50. The vectors based of PAA 15kDa had better transfection efficiency than the vectors made of PAA 65kDa. In conclusion, results of the present study indicated that grafting PAA 15kDa with high percentages of hexyl acrylate can help to prepare vectors with better transfection efficiency and less cytotoxicity.
authors: Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors: Reza Kazemi
authors: RK
authors: Oskuee
authors: School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors: Fatemeh
authors: F
authors: Dosti
authors: Targeted Drug Delivery Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors: Leila
authors: L
authors: Gholami
authors: Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: malaekehb@mums.ac.ir.
authors: Bizhan
authors: B
authors: Malaekeh-Nikouei
mesh_terms: D000818:Animals; D002412:Cations / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D004247:DNA / Q000378:metabolism*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D008970:Molecular Weight; D010316:Particle Size; D011073:Polyamines / Q000009:adverse effects* / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D014162:Transfection / Q000379:methods
chemical_list: D002412:Cations; D011073:Polyamines; D011108:Polymers; C063994:polyallylamine; D011094:Polyethyleneimine; D004247:DNA
keywords: Acrylate; Cytotoxicity; Gene delivery; Non-viral vectors; Polyallylamine; Transfection