title: Alkyl cross-linked low molecular weight polypropyleneimine dendrimers as efficient gene delivery vectors.
abstract: OBJECTIVE
  In recent years, polypropyleneimine (PPI) dendrimers have attracted great interest as non-viral gene delivery systems because of their attractive features including highly branched architecture with number of reactive end groups. However, without being structurally modified, they are not efficient gene carriers. In the present study, generation 2 and 3 (G2 and G3) of PPI dendrimers were conjugated with alkylcarboxylate groups as linker to enhance the transfection efficiency while maintaining their low cell toxicity.
  
  
  METHODS
  First, 10-bromodecanoic acid was covalently attached to all available surface primary amines of PPI G2 and G3 to increase their lipophilicity. In the subsequent step, PPIs were conjugated to the alkylcarboxylate groups of alkylcarboxylate-PPI derivatives to increase the number of surface primary amines. Physicochemical properties of modified PPIs were determined. Transfection experiments (using both luciferase and green fluorescent protein (GFP)- expressing plasmids) and cytotoxicity assay were performed to evaluate the efficiency of the final derivatives.
  
  
  RESULTS
  Fabricated vectors condensed DNA effectively so that polyplexes with appropriate size (below 155 nm) and positive surface charge were constructed. Cross-linked low molecular weight PPIs (G2 or G3) with decanoate linkage increased transfection efficiency significantly while maintaining the low cytotoxicity. PPI G2 derivative exhibited increased buffering capacity which is believed to be responsible for better proton sponge mechanism leading to higher transfection efficiency.
  
  
  CONCLUSIONS
  Our results indicated that oligomerization of low molecular weight PPI (PPI G2-alkyl-PPI G2 conjugate) could be an approach to increase the transfection efficiency and to lower the cytotoxicity of low molecular weight polycations.
authors.affiliation: Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Faezeh Moghadam
authors.initials: FM
authors.lastname: Ariaee
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.affiliation: Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Sara Amel
authors.initials: SA
authors.lastname: Farzad
authors.affiliation: Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Khalil
authors.initials: K
authors.lastname: Abnous
authors.affiliation: Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Ramezani
keywords: Alkylcarboxylate chains Gene delivery; Non-viral vectors; Polypropyleneimine