title: Adsorption of obidoxime onto human serum albumin nanoparticles: drug loading, particle size and drug release.
abstract: The standard treatment of poisoning by organophosphorous compounds such as paraoxon includes the administration of oximes. Due to their inability to rapidly cross the blood-brain barrier (BBB) in therapeutically relevant concentrations, these drugs possess insufficient activity in the central nervous system. Since human serum albumin (HSA) nanoparticles enable the delivery of a variety of drugs across the BBB into the brain, in the present study the antidote obidoxime was bound to these particles by adsorption. The resulting sorption isotherms showed a best fit to Langmuir isotherms indicating that obidoxime adsorbs to HSA nanoparticles forming a monolayer. A maximum drug loading of 93.5 microg obidoxime/mg of nanoparticles at pH 8.3 was calculated. At higher concentrations the particle diameter increased significantly with obidoxime concentration leading to instable particle systems. The in vitro release of obidoxime from HSA nanoparticles showed a rapid release of the drug from the nanoparticles within 3 h.
authors.affiliation: Institute of Pharmaceutical Technology, Goethe University, Frankfurt am Main, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Kufleitner
authors.forename: Sylvia
authors.initials: S
authors.lastname: Wagner
authors.forename: Franz
authors.initials: F
authors.lastname: Worek
authors.forename: Hagen
authors.initials: H
authors.lastname: von Briesen
authors.forename: Jörg
authors.initials: J
authors.lastname: Kreuter
mesh_terms: D000327:Adsorption; D002801:Cholinesterase Reactivators / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D009768:Obidoxime Chloride / Q000008:administration & dosage* / Q000737:chemistry; D010316:Particle Size; D012709:Serum Albumin / Q000737:chemistry*
chemical_list: D002801:Cholinesterase Reactivators; D004337:Drug Carriers; D012709:Serum Albumin; D009768:Obidoxime Chloride