title: Polyelectrolyte complex optimization for macrophage delivery of redox enzyme nanoparticles.
abstract: BACKGROUND
  We posit that cell-mediated drug delivery can improve transport of therapeutic enzymes to the brain and decrease inflammation and neurodegeneration seen during Parkinson's disease. Our prior works demonstrated that macrophages loaded with nanoformulated catalase ('nanozyme') then parenterally injected protect the nigrostriatum in a murine model of Parkinson's disease. Packaging of catalase into block ionomer complex with a synthetic polyelectrolyte block copolymer precludes enzyme degradation in macrophages.
  
  
  METHODS
  We examined relationships between the composition and structure of block ionomer complexes with a range of block copolymers, their physicochemical characteristics, and loading, release and catalase enzymatic activity in bone marrow-derived macrophages.
  
  
  RESULTS
  Formation of block ionomer complexes resulted in improved aggregation stability. Block ionomer complexes with ε-polylysine and poly(L-glutamic acid)-poly(ethylene glycol) demonstrated the least cytotoxicity and high loading and release rates. However, these formulations did not efficiently protect catalase inside macrophages.
  
  
  CONCLUSIONS
  Nanozymes with polyethyleneimine- and poly(L-lysine)(10)-poly(ethylene glycol) provided the best protection of enzymatic activity for cell-mediated drug delivery.
authors.affiliation: Center for Drug Delivery & Nanomedicine, 985830 Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Yuling
authors.initials: Y
authors.lastname: Zhao
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Haney
authors.forename: Natalia L
authors.initials: NL
authors.lastname: Klyachko
authors.forename: Shu
authors.initials: S
authors.lastname: Li
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Booth
authors.forename: Sheila M
authors.initials: SM
authors.lastname: Higginbotham
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Jones
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Zimmerman
authors.forename: R Lee
authors.initials: RL
authors.lastname: Mosley
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Kabanov
authors.forename: Howard E
authors.initials: HE
authors.lastname: Gendelman
authors.forename: Elena V
authors.initials: EV
authors.lastname: Batrakova
mesh_terms: D000818:Animals; D002374:Catalase / Q000008:administration & dosage* / Q000378:metabolism; D002417:Cattle; D002460:Cell Line; D002470:Cell Survival; D002478:Cells, Cultured; D016503:Drug Delivery Systems / Q000379:methods*; D008264:Macrophages / Q000166:cytology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009474:Neurons / Q000166:cytology; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism; D011094:Polyethyleneimine / Q000737:chemistry / Q000378:metabolism; D011099:Polyglutamic Acid / Q000737:chemistry / Q000378:metabolism; D011107:Polylysine / Q000737:chemistry / Q000378:metabolism
chemical_list: D011107:Polylysine; D011099:Polyglutamic Acid; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D002374:Catalase