The blood-brain barrier has an important biological function, protecting the brain from possible toxins in the blood, providing nutrients to brain tissue, and filtering harmful compounds from the brain back into the bloodstream. In addition to all these functions, it is also a physiological barrier that prevents the vast majority of drugs from reaching the brain, which makes it an obstacle to the development of effective drugs against neurodegenerative diseases.
Most of the traditional cell culture methods used to study drug behavior do not adequately replicate the physiology of patients. On the other hand, animal models often do not generate results comparable to the response in humans, in addition to the ethical problems that are intrinsically associated with animal experimentation.
This ‘organ-on-a-chip’ makes it possible to study the functioning of the human blood-brain barrier against drugs and to select the most effective ones
In this context, the so-called organ-on-a-chip (OoC) platforms present themselves as an excellent alternative to traditional study methods, since they allow simulating the functioning of specific human organs on a microscopic scale. These systems help to research drugs and diseases faster, cheaper and without the use of animals.
Now, researchers from the Institute of Bioengineering of Catalonia (IBEC) describe, in the Journal of Nanobiotechnology, the development of an organ on a chip that works as a model of the human blood-brain barrier. The system makes it possible to study the functioning of this barrier to drugs and track the most effective ones, avoiding testing on animals.
The system is highly versatile and opens the door to the study of on-chip pathological processes. According to one of the authors, Anna Lagunas, “the device could also be adapted to different types of studies involving the pathology of the human brain, as is the case of many neurodegenerative diseases, in which the integrity of the blood-brain barrier is at risk.” often compromised. Furthermore, if, for example, patient-derived cells were incorporated into the chip, this would allow for a personalized study of the disease.”
The system has been validated with gold nanoparticles that facilitate drug permeation across the barrier and then degrade beta-amyloid fibers associated with Alzheimer’s disease.
In turn, co-author Mònica Mir, also a researcher at the IBEC and professor at the University of Barcelona (UB), highlights: “The physical characteristics of the device make it portable, easy to use and can be subjected to mass production and automation of optical readings and electrical for a future industrial implementation”.
To validate the operation of the chip, a nanometric drug release system previously developed by Marcelo J. Kogan’s group, from the University of Chile, co-author of the article, was used.
They are gold nanoparticles that, in the first place, facilitate the permeation of the drug through the blood-brain barrier, and then bind to the so-called beta-amyloid fibers, molecules that are formed in Alzheimer’s disease, breaking them down.
How does this organ-on-a-chip work?
The device is built on a microfluidic system, which allows the manipulation and control of fluids on a very small scale and the analysis of small volume samples.
It includes a three-dimensional culture of different types of cells of human origin that form an endothelial barrier structure, which has the function of separating the blood from adjacent tissues. This structure mimics the human blood-brain barrier and has better permeability values than current standard models.
The device is manufactured in a microfluidic system and includes a culture of cells of human origin that form an endothelial barrier structure.
The model also incorporates a microelectrode system that allows monitoring the integrity and permeability of the endothelial barrier before and after drug administration.
Sujey Palma, doctoral student at IBEC and first author of the study, concludes: “It is undoubtedly a platform with great potential to be able to adequately assess the permeability of promising new therapeutic candidates such as nanosystems. Furthermore, such a device may allow us to study how these new systems may affect the post-administration barrier morphologically and physiologically.”
Researchers at the Institute of Bioengineering of Catalonia who participated in the study. /IBEC
Reference:
Sujey Palma-Florez et al. “BBB-on-a-chip with integrated micro-TEER for permeability assessment of multifunctionalized gold nanorods against Alzheimer’s disease”. Journal of Nanobiotechnology, 2023.
The work was led by the Nanobioengineering group at IBEC, directed by Josep Samitier, and the authors of the center belong to the Centro de Pesquisa Biomédica em Rede (CIBER-BBN). The study also had the participation of the University of Barcelona and the Advanced Center for Chronic Diseases in Chile.