Identifying Iron Oxide Based Materials that Can Either Pass or Not Pass through the in vitro Blood-Brain Barrier
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Identifying Iron Oxide Based Materials that Can Either Pass or Not Pass through the in vitro Blood-Brain Barrier Di Shi1, Linlin Sun2, Gujie Mi1, Soumya Bhattacharya3, Suprabha Nayar3, Thomas J Webster4 1 Department of Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USA. 2 Department of Bioengineering, Northeastern University, Boston, MA 02115, USA. 3 Materials Science and Technology Division, CSIR-National Metallurgical Laboratory, Jamshedpur, JH 831007, India. 4 Department of Chemical Engineering, Northeastern University, Boston, MA 02115, USA. ABSTRACT In this study, an in vitro blood-brain barrier model was developed using murine brain endothelioma cells (b.End3 cells). By comparing the permeability of FITC-Dextran at increasing exposure times in serum-free medium to such values in the literature, we confirm that the blood-brain barrier model was successfully established. After such confirmation, the permeability of five ferrofluid (FF) nanoparticle samples, GGB (ferrofluid synthesized using glycine, glutamic acid and BSA), GGC (glycine, glutamic acid and collagen), GGP (glycine, glutamic acid and PVA), BPC (BSA, PEG and collagen) and CPB (collagen, PVA and BSA), was determined using this model. In addition, all the five FF samples were characterized by zeta potential to determine their charge as well as TEM and dynamic light scattering for determining their hydrodynamic diameter. Results showed that FF coated with collagen had better permeability to the blood-brain barrier than FF coated with glycine and glutamic acid based on an increase of 4.5% in permeability. Through such experiments, magnetic nanomaterials, such as ferrofluids, that are less permeable to the blood brain barrier can be used to decrease neural tissue toxicity and magnetic nanomaterials with more permeable to the blood-brain barrier can be used for brain drug delivery. INTRODUCTION As we know, the blood-brain barrier act as a sanctuary that separates somatic circulating blood from the cerebrospinal fluid in the central nervous system (CNS). Consisting of tight junctions that lie between endothelial cells in capillaries in the CNS, it keeps large or hydrophilic microorganisms and molecules from passing into the cerebrospinal fluid. Unfortunately, limited by current technologies, delivering therapeutic agents or image molecules into the brain is also blocked by these highly selective tight junctions [1-3]. However, previous research has demonstrated that small lipid-soluble-molecules which have a molecular weight less than 600 Da can be transported across the blood-brain barrier, suggesting a pathway to design novel nanoparticles which can either be inhibited or promoted to cross the blood brain barrier. Nonetheless, for neural drug delivery applications, a requirement of nanoparticlebased molecules is that they can be successfully transported across the blood-brain barrier [4]. In contrast, for whole body MRI applications, there is a requirement to keep such magnetic nanoparticles from crossing the blood brain barrier in or
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