title: Nanoparticulate transport of oximes over an in vitro blood-brain barrier model.
abstract: BACKGROUND
  Due to the use of organophosphates (OP) as pesticides and the availability of OP-type nerve agents, an effective medical treatment for OP poisonings is still a challenging problem. The acute toxicity of an OP poisoning is mainly due to the inhibition of acetylcholinesterase (AChE) in the peripheral and central nervous systems (CNS). This results in an increase in the synaptic concentration of the neurotransmitter acetylcholine, overstimulation of cholinergic receptors and disorder of numerous body functions up to death. The standard treatment of OP poisoning includes a combination of a muscarinic antagonist and an AChE reactivator (oxime). However, these oximes can not cross the blood-brain barrier (BBB) sufficiently. Therefore, new strategies are needed to transport oximes over the BBB.
  
  
  RESULTS
  In this study, we combined different oximes (obidoxime dichloride and two different HI 6 salts, HI 6 dichloride monohydrate and HI 6 dimethanesulfonate) with human serum albumin nanoparticles and could show an oxime transport over an in vitro BBB model. In general, the nanoparticulate transported oximes achieved a better reactivation of OP-inhibited AChE than free oximes.
  
  
  CONCLUSIONS
  With these nanoparticles, for the first time, a tool exists that could enable a transport of oximes over the BBB. This is very important for survival after severe OP intoxication. Therefore, these nanoparticulate formulations are promising formulations for the treatment of the peripheral and the CNS after OP poisoning.
authors.affiliation: Department of Cell Biology and Applied Virology, Fraunhofer Institute for Biomedical Engineering, Sankt Ingbert, Germany.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Wagner
authors.forename: Jürgen
authors.initials: J
authors.lastname: Kufleitner
authors.forename: Anja
authors.initials: A
authors.lastname: Zensi
authors.forename: Miriam
authors.initials: M
authors.lastname: Dadparvar
authors.forename: Sascha
authors.initials: S
authors.lastname: Wien
authors.forename: Judith
authors.initials: J
authors.lastname: Bungert
authors.forename: Tikva
authors.initials: T
authors.lastname: Vogel
authors.forename: Franz
authors.initials: F
authors.lastname: Worek
authors.forename: Jörg
authors.initials: J
authors.lastname: Kreuter
authors.forename: Hagen
authors.initials: H
authors.lastname: von Briesen
mesh_terms: D000109:Acetylcholine / Q000737:chemistry; D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001812:Blood-Brain Barrier; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D002801:Cholinesterase Reactivators / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry; D036103:Nanotechnology / Q000379:methods*; D010755:Organophosphates / Q000737:chemistry; D010091:Oximes / Q000737:chemistry* / Q000494:pharmacology; D011726:Pyridinium Compounds / Q000494:pharmacology*; D012709:Serum Albumin / Q000737:chemistry; D013552:Swine
chemical_list: D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D010755:Organophosphates; D010091:Oximes; D011726:Pyridinium Compounds; D012709:Serum Albumin; D000110:Acetylcholinesterase; C022870:asoxime chloride; D000109:Acetylcholine