title: Effects of dendrimer/cyclodextrin conjugates as gene transfer carriers on nitric oxide production from macrophages.
abstract: OBJECTIVE
  The development of safe gene transfer carriers with high transfection efficiency, which does not affect the cell function, is a challenging issue. In this study, we examined the effects of α-cyclodextrin (α-CyD)/dendrimer conjugate (α-CDE (G3)) on nitric oxide (NO) production in murine macrophages J774.1 cells stimulated with toll-like receptors (TLR) ligands.
  
  
  METHODS
  NO production from macrophages stimulated with TLR ligands was determined by the Griess method. Transfection efficiency of α-CDE (G3)/plasmid DNA (pDNA) complex was quantified by a luminometer.
  
  
  RESULTS
  α-CDE (G3) significantly inhibited NO production from J774.1 cells stimulated with TLR ligands. α-CyD molecules in α-CDE (G3) had no effect on NO production. The inhibitory effect of α-CDE (G3) on NO production might be attributed to the dendrimer (G3). Increasing the degree of substitution (DS) of α-CyD in the α-CDE (G3) molecule was accompanied by a significant decrease in the inhibition of NO production. Furthermore, higher gene transfection efficiency of α-CDE (G3)/pDNA complex was observed upon increasing the DS of α-CyD.
  
  
  CONCLUSIONS
  α-CDE (G3) with high DS value of α-CyD may be considered as a safe gene transfer carrier that does not adversely affect NO production from macrophages stimulated with TLR ligands.
authors.affiliation: Department of Physical Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Motoyama
authors.affiliation: Department of Physical Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Asumi
authors.initials: A
authors.lastname: Sako
authors.affiliation: Department of Physical Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.|Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
authors.forename: Irhan
authors.initials: I
authors.lastname: Ibrahim Abu Hashim
authors.affiliation: Department of Physical Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Taishi
authors.initials: T
authors.lastname: Higashi
authors.affiliation: Department of Physical Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.|Program for Leading Graduate Schools 'HIGO (Health life science: Interdisciplinary and Glocal Oriented) Program', Kumamoto University, Kumamoto, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Arima
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D050091:Dendrimers / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D008024:Ligands; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D051193:Toll-Like Receptors / Q000819:agonists / Q000378:metabolism; D014162:Transfection / Q000379:methods*; D047391:alpha-Cyclodextrins / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*
chemical_list: D050091:Dendrimers; D008024:Ligands; D009573:Nitrites; C104700:PAMAM Starburst; D051193:Toll-Like Receptors; D047391:alpha-Cyclodextrins; D009569:Nitric Oxide
keywords: cyclodextrin; dendrimer; gene transfer carrier; nitric oxide; toll-like receptor ligands