Monical Mir

Barcelona Institute for Science and Technology, Spain

Title: Fabrication of a microfluidic platform for the assessment of permeability across the blood-brain barrier of nanotherapeutic agents for Alzheimer's disease

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Biography

Monica Mir received the Degree in Chemistry in 1998 and in 2006 her PhD in biotechnology. She realized different predoctoral stages in Greece and UK. From 2007, she held a postdoctoral position in Max Planck Institute, Germany. Since 2008, she joins the Institute for Bioengineering of Catalonia (IBEC), as Senior CIBER researcher, combined with her teaching as associate professor in the University of Barcelona. Along her carrier she was managing European, National and industrial research projects, supervising PhD students and collaborating in congresses as scientific committee. Her main interests are electrochemical biosensor, point-of-care technologies, implantable-sensors and organ-on-a-chip for biomedical applications.

Abstract

Alzheimer’s disease (AD) is a chronic neurodegenerative disorder associated to the accumulation of toxic aggregates of amyloid ? peptide (A?) in the brain that produce oxidative stress and neurotoxicity. Therefore, new therapeutic agents have being developed for AD’s treatment based on the disaggregation of A? cumulates. However, most of them do not reach the action site due the strict permeability in the brain by the blood brain barrier (BBB).

Nanotechnology is a cutting-edge field that extends different possibilities for the diagnosis and treatment of AD. In this direction, a nanosystem for AD treatment was reported that consists in gold nanorods (GNRs) functionalized with polyethylene glycol (PEG), a ? sheet breaker peptide (D1) and a peptide to shuttling through the BBB (Angiopep-2). The results revealed that the GNRs-PEG-Ang2/D1 nanosystem inhibited A? growth in vitro and decreased the toxicity of A? aggregates in an in vivo model. However, it is required to evaluate the permeability of promising therapy agents quickly and easily. BBB-on-a-chip is an interesting platform due their versatile and lower cost design to mimic both in vivo physiological and pathological conditions for the study of drug permeability.

In this work, we synthetized and characterized GNR-PEG-Ang2/D1 by absorption spectrophotometry, dynamic light scattering, laser Doppler micro-electrophoresis and transmission electron microscopy. Then, BBB-on-a-chip device was fabricated consisting in a neural chamber with human astrocytes and pericytes and a lateral channel with human brain endothelial cells in order to mimic the BBB. We determined the cytotoxic effect of GNR-PEG-Ang2/D1 over the above mentioned cells. Finally, the permeability of the nanosystems was evaluated through the BBB-on-a-chip device by confocal microscopy. The results confirm that GNR-PEG-Ang2/D1 was successfully synthetized and functionalized with the peptide Angiopep-2 and D1. In addition, GNR-PEG-Ang2/D1 showed non-toxic effect for the tri-culture at the given range of concentration for 24 hours. BBB-in-a-chip results showed the development of tight junctions between the adjacent endothelial cells in the chip which are crucial for permeability assays. Lastly, GNRs permeability assay revealed differences between the chip control and the chip exposure to GNRs.