Blood–brain barrier transport studies, aggregation, and molecular dynamics simulation of multiwalled carbon nanotube functionalized with fluorescein isothiocyanate

Sergey Shityakov,1 Ellaine Salvador,1 Giorgia Pastorin,2 Carola Förster1 1Department of Anaesthesia and Critical Care, University of Würzburg, Würzburg, Germany; 2Department of Pharmacy, National University of Singapore, Singapore 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. Keywords: blood–brain barrier, multiwalled carbon nanotube, fluorescein isothiocyanate, Transwell® system, aggregation, fluorescence microscopy, molecular dynamics