title: Surface-engineered nanoliposomes by chelating ligands for modulating the neurotoxicity associated with β-amyloid aggregates of Alzheimer's disease.
abstract: OBJECTIVE
  To develop chelating ligand-bound nanoliposomes (NLPs) for the prevention and reversal of β-Amyloid (Aβ) aggregation associated with promoting neurotoxicity in Alzheimer disease (AD).
  
  
  METHODS
  Four different chelating ligands (CuAc, EDTA, histidine and ZnAc) were surface-engineered onto NLPs using either covalent or non-covalent conjugation. Successful conjugation of chelating ligands onto the surface of NLPs was confirmed by characterization studies: SEM, TEM and FTIR analysis. Chelation energetics of EDTA with Cu(II)/Zn(II)-Aβ(10-21) and nanoformation of emulsified polymers were computed and corroborated with experimental and analytical data using chemometric molecular modeling.
  
  
  RESULTS
  The modified NLPs produced were spherical in shape, 127-178 nm in size, with polydispersity index from 0.217-0.920 and zeta potential range of -9.59 to -37.3 mV. Conjugation efficiencies were 30-76 %, which confirmed that chelating ligands were attached to the NLP surface.
  
  
  CONCLUSIONS
  In vitro and ex vivo results elucidated the effectiveness of chelating ligand-bound NLPs for prevention of CuAβ(1-42) or ZnAβ(1-42) aggregate buildup associated with neurotoxicity in PC12 neuronal cells, as well as promotion of intracellular uptake in the presence of Cu(II) or Zn(II) metal ions.
authors.affiliation: Faculty of Health Sciences, Department of Pharmacy & Pharmacology, University of Witwatersrand, Parktown, 2193, Johannesburg, South Africa.
authors.forename: Maluta S
authors.initials: MS
authors.lastname: Mufamadi
authors.forename: Yahya E
authors.initials: YE
authors.lastname: Choonara
authors.forename: Pradeep
authors.initials: P
authors.lastname: Kumar
authors.forename: Girish
authors.initials: G
authors.lastname: Modi
authors.forename: Dinesh
authors.initials: D
authors.lastname: Naidoo
authors.forename: Valence M K
authors.initials: VM
authors.lastname: Ndesendo
authors.forename: Lisa C
authors.initials: LC
authors.lastname: du Toit
authors.forename: Sunny E
authors.initials: SE
authors.lastname: Iyuke
authors.forename: Viness
authors.initials: V
authors.lastname: Pillay
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000008:administration & dosage / Q000737:chemistry*; D003300:Copper / Q000378:metabolism; D008024:Ligands; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry*; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D016716:PC12 Cells; D010316:Particle Size; D051381:Rats; D015032:Zinc / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D002614:Chelating Agents; D008024:Ligands; D008081:Liposomes; D003300:Copper; D015032:Zinc