title: Comparison of generation 3 polyamidoamine dendrimer and generation 4 polypropylenimine dendrimer on drug loading, complex structure, release behavior, and cytotoxicity.
abstract: BACKGROUND
  Polyamidoamine (PAMAM) and polypropylenimine (PPI) dendrimers are the commercially available and most widely used dendrimers in pharmaceutical sciences and biomedical engineering. In the present study, the loading and release behaviors of generation 3 PAMAM and generation 4 PPI dendrimers with the same amount of surface amine groups (32 per dendrimer) were compared using phenylbutazone as a model drug.
  
  
  METHODS
  The dendrimer-phenylbutazone complexes were characterized by (1)H nuclear magnetic resonance and nuclear Overhauser effect techniques, and the cytotoxicity of each dendrimer was evaluated.
  
  
  RESULTS
  Aqueous solubility results suggest that the generation 3 PAMAM dendrimer has a much higher loading ability towards phenylbutazone in comparison with the generation 4 PPI dendrimer at high phenylbutazone-dendrimer feeding ratios. Drug release was much slower from the generation 3 PAMAM matrix than from the generation 4 PPI dendrimer. In addition, the generation 3 PAMAM dendrimer is at least 50-fold less toxic than generation 4 PPI dendrimer on MCF-7 and A549 cell lines.
  
  
  CONCLUSIONS
  Although the nuclear Overhauser effect nuclear magnetic resonance results reveal that the generation 4 PPI dendrimer with a more hydrophobic interior encapsulates more phenylbutazone, the PPI dendrimer-phenylbutazone inclusion is not stable in aqueous solution, which poses a great challenge during drug development.
authors.affiliation: School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Naimin
authors.initials: N
authors.lastname: Shao
authors.forename: Yunzhang
authors.initials: Y
authors.lastname: Su
authors.forename: Jingjing
authors.initials: J
authors.lastname: Hu
authors.forename: Jiahai
authors.initials: J
authors.lastname: Zhang
authors.forename: Hongfeng
authors.initials: H
authors.lastname: Zhang
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Cheng
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D050091:Dendrimers / Q000737:chemistry* / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D010653:Phenylbutazone / Q000493:pharmacokinetics; D011126:Polypropylenes / Q000737:chemistry* / Q000494:pharmacology; D012995:Solubility
chemical_list: D050091:Dendrimers; D004337:Drug Carriers; C104700:PAMAM Starburst; D011126:Polypropylenes; C443641:poly(propyleneimine); D010653:Phenylbutazone