title: Hydrophobically modified low molecular weight chitosans as efficient and nontoxic gene delivery vectors.
abstract: BACKGROUND
  Chitosan derivatives are potential candidates for gene delivery because they are biocompatible and low toxic. However, their use has been limited by their moderate transfection efficiency and the rather large sizes of DNA complexes with high molecular weight chitosans. To circumvent these limitations, we used low molecular weight (approximately 5 kDa) chitosans grafted at 3 and 18 mol% with N-/2(3)-(dodec-2-enyl)succinoyl groups (HM-LMW-ch) that exhibit surfactant-like properties.
  
  
  METHODS
  The physico-chemical properties of complexes of DNA with the two HM-LMW-ch derivatives and the nonmodified LMW-ch were compared by electrophoresis, dynamic light scattering, fluorescence spectroscopy and fluorescence correlation spectroscopy. Moreover, their transfection efficiencies and cytotoxicity were evaluated and their intracellular trafficking was monitored by confocal microscopy. Finally, their ability to deliver genes in mice kidneys after systemic administration was investigated.
  
  
  RESULTS
  Complexes with HM(3%)-LMW-ch, but not with HM(18%)-LMW-ch and LMW-ch, efficiently delivered genes in mice kidneys. HM(3%)-LMW-ch formed small positively charged particles that were resistant to DNases and nucleases and marginally interact with serum components. Moreover, these particles were efficiently internalized in cells and low toxic. By contrast, HM(18%)-LMW-ch formed large and weakly charged aggregates with DNA that were highly susceptible to DNases and nucleases.
  
  
  CONCLUSIONS
  HM(3%)-LMW-ch appears to be a promising nonviral vector with low cytotoxicity and efficient transfection properties.
authors.affiliation: Département de Pharmacologie and Physicochimie, Equipe Photophysique des Interactions Biomoléculaires, Institut Gilbert Laustriat, Faculté de Pharmacie, Université Louis Pasteur, Illkirch, France.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Sebnem
authors.initials: S
authors.lastname: Ercelen
authors.forename: Guy
authors.initials: G
authors.lastname: Duportail
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Schaub
authors.forename: Vladimir
authors.initials: V
authors.lastname: Tikhonov
authors.forename: Alexander
authors.initials: A
authors.lastname: Slita
authors.forename: Vladimir
authors.initials: V
authors.lastname: Zarubaev
authors.forename: Valery
authors.initials: V
authors.lastname: Babak
authors.forename: Yves
authors.initials: Y
authors.lastname: Mély
mesh_terms: D000818:Animals; D048271:Chitosan / Q000737:chemistry* / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry* / Q000627:therapeutic use; D015316:Genetic Therapy / Q000379:methods; D057927:Hydrophobic and Hydrophilic Interactions; D007668:Kidney / Q000378:metabolism; D051379:Mice; D008970:Molecular Weight; D014162:Transfection / Q000379:methods* / Q000592:standards
chemical_list: D004337:Drug Carriers; D048271:Chitosan