Lab-On-A-Chip for the Development of Pro-/Anti-Angiogenic Nanomedicines to Treat Brain Diseases

Abstract

There is a huge demand for pro-/anti-angiogenic nanomedicines to treat conditions such as ischemic strokes, brain tumors, and neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Nanomedicines are therapeutic particles in the size range of 10–1000 nm, where the drug is encapsulated into nano-capsules or adsorbed onto nano-scaffolds. They have good blood–brain barrier permeability, stability and shelf life, and able to rapidly target different sites in the brain. However, the relationship between the nanomedicines’ physical and chemical properties and its ability to travel across the brain remains incompletely understood. The main challenge is the lack of a reliable drug testing model for brain angiogenesis. Recently, microfluidic platforms (known as “lab-on-a-chip” or LOCs) have been developed to mimic the brain micro-vasculature related events, such as vasculogenesis, angiogenesis, inflammation, etc. The LOCs are able to closely replicate the dynamic conditions of the human brain and could be reliable platforms for drug screening applications. There are still many technical difficulties in establishing uniform and reproducible conditions, mainly due to the extreme complexity of the human brain. In this paper, we review the prospective of LOCs in the development of nanomedicines for brain angiogenesis–related conditions.

Angiogenesis and Functional Vessel Formation Induced by Interstitial Flow and Vascular Endothelial Growth Factor Using a Microfluidic Chip

“…Microfluidic chips have emerged as an important technology for biomimicry of the cellular microenvironment in vivo [24]. Functional vessel models constructed using the microfluidic technique can be employed for various functional tests such as the effect of blood flow on endothelial cells, cancer angiogenesis and intravasation, and the screening of anti-angiogenesis drugs [25][26][27][28][29]. Blood vessel sprouting and even lymphatic vessel sprouting have been reproduced on these microfluidic models [30,31].…”

Recent Developments in Microfluidic Technologies for Central Nervous System Targeted Studies

“…As previously discussed in prior sections, microfluidic devices are able to emulate brain microvasculature-related events, for instance, angiogenesis, inflammation or BBB changes [79]. It is known that BBB dysfunction underlies the development of NDs.…”

“…It is known that BBB dysfunction underlies the development of NDs. By reconstituting such dynamic conditions of the human brain, a validated BBB-on-a-chip can be used to address the critical need to improve the understanding of the pathological mechanisms of NDs [32,79]. Furthermore, since CNS models that mimic NDs typically require controllable fluid delivery and long-term culture duration, microfluidics come forth as an advantageous and reliable platform to study these disorders [39].…”

Theragnostic nanomotors: Successes and upcoming challenges

“…The next avatar of organoid cultures-body-on-chip systems, connect multiorgan culture systems through microfluidics to afford an experimental simulation of the connected physiologically active anatomies of multicellular organisms (Marx et al, 2012;Materne et al, 2015;Shupe et al, 2020). Such experimental platforms will become inevitable testing grounds for the study of biodistribution and efficiency of NMs to penetrate and theragnose tissue pathologies (Parimalam et al, 2019;Zhang et al, 2010). Discovery of earlier anticipated adverse effects of such modalities has already begun to being unraveled through harnessing such multiorgan platforms, a case in point being the demonstrated hepatotoxic effects of 50 nm carboxylated polystyrene nanoparticles tested within a gut-liver chip platform (Esch et al, 2014).…”