title: In vivo brain microdialysis to evaluate FITC-dextran encapsulated immunopegylated nanoparticles.
abstract: BACKGROUND
  Delivery of drugs and dyes through intact blood-brain barrier (BBB) is extremely sought-after. A safe and reliable measurement of delivery efficacy in live animals is necessary.
  
  
  OBJECTIVE
  To investigate the brain uptake of FITC-dextran MW 4000 (FD4) by CD71/OX-26 coated nanoparticles by microdialysis sampling and fluorescence/confocal microscopy.
  
  
  METHODS
  Methoxy-poly(ethylene glycol)-poly(lactide) (Met-PEG-PLA) and maleimide-poly(ethylene glycol)-poly(lactide) (Mal-PEG-PLA) nanoparticles were prepared by nanoprecipitation. The surfaces of the prepared nanoparticles were embellished with CD-71/OX-26 antibodies for brain targeting. Male Sprague Dawley rats received 0.4 mg/kg FD4 and equivalent nanoparticulate formulation through lateral tail vein. Animals were euthanized 24 h postadministration, after which the tissues were harvested and analyzed for FD4 concentrations. Tissues were fixed with paraformaldehyde, cryotomed to 20 µm sections, and analyzed by Total Internal Reflection microscopy.
  
  
  RESULTS
  Particle sizes of 200 ± 25 nm and zeta potentials of -18 ± 1 mV were obtained. FD4 concentrations, determined using in vivo brain microdialysis, were high on the first day (~360 ng/mL) compared to 60 ng/mL on the following 2 days. The nanoparticle treated animals showed significantly higher (p < 0.05) FD4 concentrations in the brain than pure-FD4 treated animals. Immunopegylated nanoparticles sustained and enhanced Central nervous system (CNS) concentration of hydrophilic dye for at least 3 days.
  
  
  CONCLUSIONS
  Immunopegylated nanoparticles produce enhanced and sustained uptake of brain permeability marker FD4 relative to controls.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, St. John's University, Jamaica, NY 11439, USA. bommana.murali@gmail.com
authors.forename: Murali Mohan
authors.initials: MM
authors.lastname: Bommana
authors.forename: Bharat
authors.initials: B
authors.lastname: Kirthivasan
authors.forename: Emilio
authors.initials: E
authors.lastname: Squillante
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D003911:Dextrans / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D016650:Fluorescein-5-isothiocyanate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008301:Maleimides / Q000737:chemistry; D017551:Microdialysis; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D053758:Nanoparticles; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D011990:Receptors, Transferrin / Q000276:immunology; D015203:Reproducibility of Results; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C068126:CD71 antigen; D003911:Dextrans; D004337:Drug Carriers; D008301:Maleimides; D011091:Polyesters; D011990:Receptors, Transferrin; C015219:fluorescein isothiocyanate dextran; C492425:methoxy poly(ethylene glycol)-poly(lactide); C043592:maleimide; D011092:Polyethylene Glycols; D016650:Fluorescein-5-isothiocyanate