Vascularized tissue drug screening
Brand: Aracari Biosciences
Currently, to bring a new drug or biologic to market requires 10-12 years and $2.6B. Of the total development costs, about 60% is spent on human clinical trials, which can take up to 8 years and $1.5B. Despite this significant investment, over 99% of drug candidates ultimately fail due to lack of efficacy or unexpected toxicities. Many of these failures can be directly attributed to the limitations of current pre-clinical testing models.
Aracari’s patented Vascularized Micro-Organ (VMOTM), Vascularized Micro-Tumor (VMTTM), and Vascularized Micro-Brain (VMBTM) devices faithfully recreate complex 3D cellular structures embedded in a natural matrix, where oxygen, nutrients, and cells (e.g., leukocytes) are transported through naturally-forming, dynamic, human blood vessels. The result is an enhanced drug discovery pipeline that encourages a “fail early, fail cheap” strategy, and thus significantly reduces costs by more accurately identifying candidate drugs for clinical trial.
Life On a Chip
Learn how our proprietary 3D Vascularized Micro-Organ™ (VMO™), Vascularized Micro-Tumor™ (VMT™) and Vascularized Micro-Brain™ (VMB™) platforms can help launch a new era of drug discovery and precision medicine.
Vascular ToxicityAracari Vascularized Micro-Organ (VMOTM) platform is well suited for investigating vascular toxicities. Drugs of interest flow through the vasculature at rates comparable to those seen in vivo, and metabolites, cytokines and other biomarkers released by the endothelial cells can be collected for further analysis. The platform also allows for real-time imaging of the vessel morphology. The vascular network can be fixed and stained in situ, or harvested for gene expression studies (qPCR, RNAseq, single cell RNAseq). Additionally, cytokine markers of activation can be collected upon flowing through the platform.
Aracari Vascularized Micro-Tumor (VMTTM) platform is well suited for investigating lead compound efficacy against tumors growing in a 3D, biomimetic environment. Drugs of interest are perfused through the vasculature and are delivered to the tumors, just as they are in vivo. Currently the different tumor models that are being offered are:
- Colon Cancer
- Breast Cancer
- Lung Cancer
- Pancreatic Cancer
Don’t see your tumor type of interest? Contact us to discuss your application and discuss additional tumor types currently under development.
The efficacy of both anti-tumor and anti-vascular drugs can be tested by direct measurement output of GFP-expressing tumor cells and by vascular network analysis. Cytokine markers of activation can be collected upon flowing through the platform. Additionally, tissues can be fixed and stained in situ for biomarker expression, or alternatively, tissues can be harvested for gene expression analysis (qPCR, RNAseq, single cell RNAseq).
Blood Brain BarrierAracari Vascularized Micro-Brain (VMBTM) platform is ideally suited for investigating delivery of drugs across the blood-brain barrier. The vascular network can be perfused with fluorophore-tagged dextrans of different molecular weight and the leak of these from the vessels in response to different stimuli can be tracked in real-time. Quantification of leak can be used to calculate permeability coefficients. In addition, drug permeability can be assessed in a number of ways. Larger molecules (such as Ig) can be fluorescently tagged and imaged directly. Alternatively, samples can be collected from the extravascular space and analyzed by ELISA or mass spectrometry. Drugs that target BBB transporter molecules such as P-glycoprotein (e.g. Elacridar) can be used to assess whether a drug is a P-gp substrate