title: PEGylation of Polypropylenimine Dendrimer with Alkylcarboxylate Chain Linkage to Improve DNA Delivery and Cytotoxicity.
abstract: One of the major limitations of effective nonviral gene carriers is their potential high cytotoxicity. Conjugation of polyethylene glycol (PEG) to polymers is a common approach to decrease toxicity and improve biodistribution. The aim of this study was to evaluate the effect of PEGylation on generation 5 polypropylenimine (PPI) dendrimer by using PEG moieties or alkyl-PEG groups. Polymers were synthesized by grafting of 5 and 10 % primary amines of PPI to NH2-PEG-COOH or Br-(CH2)9-CO-NH-PEG-COOH through Amide bond formation or nucleophilic substitution, respectively. Transfection efficiency and cytotoxicity were analyzed after 4 and 24 h exposure of neuroblastoma cell line (Neuro-2a) with synthesized vectors. Among all of the PEG-PPI derivatives, 5 % PEG-conjugated G5 PPI with alkyl chain (PPI-alkyl-PEG 5 %) resulted in the most efficient gene expression. This vector also significantly decreased the in vitro cytotoxicity and sub-G1 peak in flow cytometry histogram after 24 h incubation. Our results indicate that modification of 5 % primary amines of G5 PPI with PEG using alkyl chain as linker produces a promising vector combining low cytotoxicity, appropriate biodegradability, and high gene transfection efficiency.
authors.affiliation: Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Hashemi
authors.forename: Sara
authors.initials: S
authors.lastname: Ayatollahi
authors.forename: Hamideh
authors.initials: H
authors.lastname: Parhiz
authors.forename: Ahad
authors.initials: A
authors.lastname: Mokhtarzadeh
authors.forename: Soheila
authors.initials: S
authors.lastname: Javidi
authors.forename: Mohammad
authors.initials: M
authors.lastname: Ramezani
mesh_terms: D000818:Animals; D017209:Apoptosis; D002264:Carboxylic Acids / Q000737:chemistry*; D045744:Cell Line, Tumor; D050091:Dendrimers / Q000737:chemistry*; D004912:Erythrocytes / Q000378:metabolism; D004996:Ethidium / Q000378:metabolism; D006801:Humans; D051379:Mice; D010316:Particle Size; D011073:Polyamines / Q000138:chemical synthesis / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy; D017550:Spectroscopy, Fourier Transform Infrared; D055672:Static Electricity; D014162:Transfection
chemical_list: D002264:Carboxylic Acids; D050091:Dendrimers; D011073:Polyamines; C522250:polyethylene glycol-poly(propylene imine); D011092:Polyethylene Glycols; D004996:Ethidium