Microchip-based Delivery System Development

Drug delivery remains a challenge for the treatment of brain tumor diseases and drug candidate development, with the main challenge being the presence of the blood-brain barrier (BBB), which limits drug entry into the brain parenchyma. The BBB serves as a functional physical barrier regulating both passive and active transport, as well as a metabolic and immune barrier. The BBB typically allows only those molecules that are lipophilic and of low molecular weight (less than 400-500 Da) to enter the brain via the trans-cellular pathway from the bloodstream to the brain, thus limiting drug delivery.

Figure 1. Proportions of the blood–brain barrier. (Banks, W., 2016)

We offer microchip-based brain tumor drug delivery system development services

In addition to developing drug delivery systems using nanoparticle drug carriers for brain tissue, Alfa Cytology is also developing microchip-based drug delivery systems for brain tumors. We use microfluidic chip technology to build in vitro BBB systems that are easily modulated and close to the body's microenvironment. Microfluidic chips are micro response chambers, microchannels, and other functional units integrated into a chip of a few square centimeters (or even smaller). We manipulate microfluidics by connecting these functional units and channel networks to enable sample preparation, reaction, separation, and detection on the chip. This can be applied to studies on the effect of blood-brain barrier function, migration of tumor cells, and permeability assessment.

Chip design

• Simulation of brain microvascular structures
• Simulation of neurovascular unit (NVU) structure

Cell culture

We use co-culture mode, which can better mimic their in vivo tissue structure and form a tighter barrier. We have established endothelial cell-astrocyte binary co-culture models as well as endothelial cell-astrocyte-pericyte, endothelial cell-astrocyte-neuron, and endothelial cell-pericyte-neuron ternary co-culture models.

BBB system analysis

• Measurement of transendothelial electrical resistance (TEER)
• Analyze permeability
• Immunostaining for known markers

Constructible cell sources: large animal cells such as bovine and porcine and rat cells, etc.

Cell types: endothelial cells, astrocytes, pericytes, neurons, and microglia

Advantages of the microchip-based BBB system we constructed

• Small functional size, material saving, and low cost
• Fast media exchange and rapid attainment of steady-state
• Provides a parallel, controlled, and dynamic microenvironment
• The thinner culture membrane reduces co-culture cell spacing
• Enables high-throughput design applications
• Easy to analyze and controlled delivery of the test substance
• Can be integrated into biosensors for long-term monitoring of BBB function

How we can do better in this project

Achieving direct drug delivery to the lesion is essential for successful drug development, so drug molecules must be cell-permeable. Alfa Cytology offers services for the development of microchip-based functional BBB systems based on our accurate grasp of cutting-edge brain tumor research and our extensive experience in brain tumor research. Its micro and nanoscale match the size of cells and the confined culture approach is close to the physiological environment, simulating controlled biochemical and physical factors, which can accelerate the speed to market of new drugs you are studying. Please feel free to contact our staff with any questions for a satisfactory response.

Reference

1. Banks, W.(2016). "From blood–brain barrier to blood–brain interface: new opportunities for CNS drug delivery." Nature Reviews Drug Discovery, 15, 275-292.