Optimizing superparamagnetic iron oxide nanoparticles as drug carriers using an in vitro blood–brain barrier model

Abstract

Di Shi,1 Gujie Mi,1 Soumya Bhattacharya,2 Suprabha Nayar,2 Thomas J Webster1,3 1Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 2Materials Science and Technology Division, Council for Scientific and Industrial Research-National Metallurgical Laboratory, Jamshedpur, India; 3Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah, Saudi Arabia Abstract: In the current study, an optimized in vitro blood–brain barrier (BBB) model was established using mouse brain endothelial cells (b.End3) and astrocytes (C8-D1A). Before measuring the permeability of superparamagnetic iron oxide nanoparticle (SPION) samples, the BBB was first examined and confirmed by an immunofluorescent stain and evaluating the transendothelial electrical resistance. After such confirmation, the permeability of the following five previously synthesized SPIONs was determined using this optimized BBB model: 1) GGB (synthesized using glycine, glutamic acid, and bovine serum albumin [BSA]), 2) GGC (glycine, glutamic acid, and collagen), 3) GGP (glycine, glutamic acid, and polyvinyl alcohol), 4) BPC (BSA, polyethylene glycol, and collagen), and 5) CPB (collagen, polyvinyl alcohol, and BSA). More importantly, after the permeability test, transmission electron microscopy thin section technology was used to investigate the mechanism behind this process. Transmission electron microscopy thin section images supported the hypothesis that collagen-coated CPB SPIONs displayed better cellular uptake than glycine and glutamine acid-coated GGB SPIONs. Such experimental data demonstrated how one can modify SPIONs to better deliver drugs to the brain to treat a wide range of neurological disorders. Keywords: superparamagnetic iron oxide nanoparticles, blood–brain barrier, permeability

Keywords

• SPIONs
• blood-brain barrier
• permeability