Abstract
Neurodegenerative diseases (NDs) bear a lot of weight in public health. By studying the properties of the blood-brain barrier (BBB) and its fundamental interactions with the central nervous system (CNS), it is possible to improve the understanding of the pathological mechanisms behind these disorders and create new and better strategies to improve bioavailability and therapeutic efficiency, such as nanocarriers. Microfluidics is an intersectional field with many applications. Microfluidic systems can be an invaluable tool to accurately simulate the BBB microenvironment, as well as develop, in a reproducible manner, drug delivery systems with well-defined physicochemical characteristics. This review provides an overview of the most recent advances on microfluidic devices for CNS-targeted studies. Firstly, the importance of the BBB will be addressed, and different experimental BBB models will be briefly discussed. Subsequently, microfluidic-integrated BBB models (BBB/brain-on-a-chip) are introduced and the state of the art reviewed, with special emphasis on their use to study NDs. Additionally, the microfluidic preparation of nanocarriers and other compounds for CNS delivery has been covered. The last section focuses on current challenges and future perspectives of microfluidic experimentation.
Highlights
Neurodegenerative diseases (NDs) such as Parkinson’s disease (PD), Alzheimer’s disease (AD), Amyotrophic lateral sclerosis (ALS), Multiple sclerosis (MS) or Huntington’s disease (HD) are among the disorders with the highest incidence worldwide, with their increase alarming when it comes to the elderly population [1,2]
The results of this study suggest that hypoxia is needed to better recapitulate the native blood-brain barrier (BBB) in terms of transferrin receptor function, as well as of other BBB transporters, since when compared to normoxic conditions, hypoxic conditions resulted in enhanced differentiation and increased expression of those proteins [59]
The results showed that co-culture with astrocytes enhanced BBB integrity, and that while both human umbilical vein endothelial cells (HUVEC) and hCMEC/D3 monolayers demonstrated size-selective penetrability, the hCMEC/D3 line had significantly higher barrier integrity compared to HUVEC
Summary
Neurodegenerative diseases (NDs) such as Parkinson’s disease (PD), Alzheimer’s disease (AD), Amyotrophic lateral sclerosis (ALS), Multiple sclerosis (MS) or Huntington’s disease (HD) are among the disorders with the highest incidence worldwide, with their increase alarming when it comes to the elderly population [1,2]. By providing a highly controlled cellular microenvironment, organs-on-a-chip are suitable tools to assess the responses of the BBB to physiological and pathological stimuli, including analysis of metabolic, genetic and biochemical activities [7,10] They allow for real-time, high-resolution imaging [10]. The BBB only allows selective passage of molecules essential to the functioning of the brain, restricting the entrance of 98%, or more, of therapeutics [14] In this context, nanotechnology-based approaches such as nanoparticles (NPs) present an opportunity to rethink and retackle the adversities connected to poor BBB permeability when delivering drug candidates/diagnostic agents to the CNS. It is critical to have a better understanding and translation of the BBB physiological and pathological processes that precede and increase vulnerability to NDs, since it might offer new avenues to help identify novel strategies and therapeutic targets for drug discovery and development
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
