title: Brain-targeted delivery of doxorubicin using glutathione-coated nanoparticles for brain cancers.
abstract: OBJECTIVE
  To prepare and characterize in vitro a novel brain-targeted delivery of doxorubicin using glutathione-coated nanoparticles (NPs) for the treatment of brain cancer.
  
  
  METHODS
  Doxorubicin-loaded NPs were prepared by the nanoprecipitation method using PLGA-COOH (dl-lactide-co-glycolide). The NPs were coated with a glutathione-PEG conjugate (PEG-GSH) in order to target delivery to the brain. The NPs were characterized via in vitro studies to determine particle size, drug release, cellular uptake, immunofluorescence study, cytotoxic assay, and in vitro blood-brain barrier (BBB) assay.
  
  
  RESULTS
  The NPs showed a particle size suitable for BBB permeation (particle size around 200 nm). The in vitro release profile of the NPs exhibited no initial burst release and showed sustained drug release for up to 96 h. The immunofluorescence study showed the glutathione coating does not interfere with the drug release. Furthermore, in vitro BBB Transwell™ study showed significantly higher permeation of the doxorubicin-loaded NPs compared with the free doxorubicin solution through the coculture of rat brain endothelial (RBE4) and C6 astrocytoma cells (p < 0.05).
  
  
  CONCLUSIONS
  We conclude that the initial in vitro characterization of the NPs demonstrates potential in delivering doxorubicin to cancer cells with possible future application in targeting brain cancers in vivo.
authors.affiliation: Department of Pharmaceutical Sciences, Northeast Ohio Medical University (NEOMED) , Rootstown, OH , USA and.
authors.forename: Werner
authors.initials: W
authors.lastname: Geldenhuys
authors.forename: Daniel
authors.initials: D
authors.lastname: Wehrung
authors.forename: Anastasia
authors.initials: A
authors.lastname: Groshev
authors.forename: Anjali
authors.initials: A
authors.lastname: Hirani
authors.forename: Vijaykumar
authors.initials: V
authors.lastname: Sutariya
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism; D016503:Drug Delivery Systems; D005978:Glutathione / Q000737:chemistry* / Q000378:metabolism; D019344:Lactic Acid / Q000737:chemistry / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry* / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism; D011100:Polyglycolic Acid / Q000737:chemistry / Q000378:metabolism; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D004317:Doxorubicin; D005978:Glutathione
keywords: Brain cancer; PLGA-PEG NP; brain-targeted delivery; doxorubicin