title: Nanoparticle surface charges alter blood-brain barrier integrity and permeability.
abstract: OBJECTIVE
  The blood-brain barrier (BBB) presents both a physical and electrostatic barrier to limit brain permeation of therapeutics. Previous work has demonstrated that nanoparticles (NPs) overcome the physical barrier, but there is little known regarding the effect of NP surface charge on BBB function. Therefore, this work evaluated: (1) effect of neutral, anionic and cationic charged NPs on BBB integrity and (2) NP brain permeability.
  
  
  METHODS
  Emulsifying wax NPs were prepared from warm oil-in-water microemulsion precursors using neutral, anionic or cationic surfactants to provide the corresponding NP surface charge. NPs were characterized by particle size and zeta potential. BBB integrity and NP brain permeability were evaluated by in situ rat brain perfusion.
  
  
  RESULTS
  Neutral NPs and low concentrations of anionic NPs were found to have no effect on BBB integrity, whereas, high concentrations of anionic NPs and cationic NPs disrupted the BBB. The brain uptake rates of anionic NPs at lower concentrations were superior to neutral or cationic formulations at the same concentrations.
  
  
  CONCLUSIONS
  (1) Neutral NPs and low concentration anionic NPs can be utilized as colloidal drug carriers to brain, (2) cationic NPs have an immediate toxic effect at the BBB and (3) NP surface charges must be considered for toxicity and brain distribution profiles.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX 79106-1712, USA.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Lockman
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Koziara
authors.forename: Russell J
authors.initials: RJ
authors.lastname: Mumper
authors.forename: David D
authors.initials: DD
authors.lastname: Allen
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism*; D004337:Drug Carriers / Q000008:administration & dosage / Q000493:pharmacokinetics; D008297:Male; D049329:Nanostructures / Q000737:chemistry*; D010539:Permeability / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D055672:Static Electricity; D013499:Surface Properties
chemical_list: D004337:Drug Carriers