title: Blood-brain barrier transport studies, aggregation, and molecular dynamics simulation of multiwalled carbon nanotube functionalized with fluorescein isothiocyanate.
abstract: In this study, the ability of a multiwalled carbon nanotube functionalized with fluorescein isothiocyanate (MWCNT-FITC) was assessed as a prospective central nervous system-targeting drug delivery system to permeate the blood-brain barrier. The results indicated that the MWCNT-FITC conjugate is able to penetrate microvascular cerebral endothelial monolayers; its concentrations in the Transwell(®) system were fully equilibrated after 48 hours. Cell viability test, together with phase-contrast and fluorescence microscopies, did not detect any signs of MWCNT-FITC toxicity on the cerebral endothelial cells. These microscopic techniques also revealed presumably the intracellular localization of fluorescent MWCNT-FITCs apart from their massive nonfluorescent accumulation on the cellular surface due to nanotube lipophilic properties. In addition, the 1,000 ps molecular dynamics simulation in vacuo discovered the phenomenon of carbon nanotube aggregation driven by van der Waals forces via MWCNT-FITC rapid dissociation as an intermediate phase.
authors.affiliation: Department of Anaesthesia and Critical Care, University of Würzburg, Würzburg, Germany.
authors.forename: Sergey
authors.initials: S
authors.lastname: Shityakov
authors.affiliation: Department of Anaesthesia and Critical Care, University of Würzburg, Würzburg, Germany.
authors.forename: Ellaine
authors.initials: E
authors.lastname: Salvador
authors.affiliation: Department of Pharmacy, National University of Singapore, Singapore.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Pastorin
authors.affiliation: Department of Anaesthesia and Critical Care, University of Würzburg, Würzburg, Germany.
authors.forename: Carola
authors.initials: C
authors.lastname: Förster
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry / Q000493:pharmacokinetics; D051379:Mice; D056004:Molecular Dynamics Simulation; D037742:Nanotubes, Carbon / Q000737:chemistry / Q000633:toxicity
chemical_list: D004337:Drug Carriers; D037742:Nanotubes, Carbon; D016650:Fluorescein-5-isothiocyanate
keywords: Transwell® system; aggregation; blood–brain barrier; fluorescein isothiocyanate; fluorescence microscopy; molecular dynamics; multiwalled carbon nanotube