Trans-BBB PK Analysis in Stroke Drug Discovery and Development

The blood-brain barrier (BBB) is a complex anatomical and physiological structure composed of related structures called neurovascular units (NVUs). NVUs protect the sensitive central nervous system (CNS) from molecules with potentially toxic or adverse neurological effects. These protective mechanisms prevent the introduction of therapeutic drugs to treat CNS disorders. To have a pharmacological effect, a drug needs to cross the BBB at a sufficient concentration and interact with the target within the brain. Several (pre) drugs and nanocarriers utilizing transporter proteins have been developed to improve drug uptake in the brain. In any case, quantitatively assessing the ability of new drugs to cross the BBB is crucial for the development of drugs for stroke.

Fig. 1. A schematic illustration of the main pharmacokinetic principles of transporter-mediated drug delivery to the brain. (Puris et al., 2022)

Custom Trans-BBB PK Analysis Services

Ace Therapeutics has a team of experienced scientists who specialize in BBB research in stroke. Ace Therapeutics offers a variety of methods to analyze the ability of stroke drugs to cross the BBB from the blood stream, measure their concentration in the central nervous system, and predict their functional capacity. Our skilled research directors can help design optimal strategies and customize protocols to advance a client's stroke drug discovery program.

In Vivo Measurement of the Ability of Stroke Drugs to Cross the BBB

• Traditional Methods
  We can test the concentration of stroke drugs in brain tissue and have compared it to vascular concentrations at a single point or at different time points. Before sampling, the vascular compartment must either undergo a washout phase to ensure accurate measurement of tissue concentrations or be compared using non-absorbed materials to estimate the ratio of absorbed drug to that retained in the vessel.
• Cerebral Perfusion
  We can perform brain perfusion studies to assess the degree of stroke drugs across the BBB. We sample brain tissue immediately after perfusion and image the brain tissue using microscopic techniques to analyze the concentration of stroke medication and its location in the tissue. The brain uptake index responds to the stroke drugs that pass through the BBB.
• Imaging Techniques and Micro-dialysis Techniques
  A variety of noninvasive imaging techniques are available to assess BBB permeability in real-time. We use micro-dialysis techniques to measure concentrations in the extracellular space of the brain. In these experiments, we can insert microcatheters into the CNS in situ in a targeted manner and continuously sample the extracellular fluid to provide measurements of the concentration of stroke drugs in the CNS of awake animals.

In Vitro Measurement of the Ability of Stroke Drugs to Cross the BBB

We can construct cell culture models for BBB PK analysis. We use confocal microscopy to analyze fluorescein-labeled ligands to assess the specific binding of labeled substances to the endothelial cell surface, and monitor the efflux of labeled cotransporter proteins that are not labeled with fluorescein.

Our Advantages

• We offer a variety of assays for assessing the trans-BBB PK properties of stroke medications that can be customized to meet your needs.
• We can image the brain in animals of stroke and reliably quantify images to ensure accurate data.
• We can combine BBB PK measurements with other readings for comprehensive analysis.

Ace Therapeutics provides reliable BBB PK analysis services in stroke drug discovery and development for clients worldwide. Our experts are actively developing other assays to measure the ability of stroke drugs to cross the BBB. If you are interested in our services, please do not hesitate to contact us!

1. Puris, E., et al. (2022). Targeting transporters for drug delivery to the brain: can we do better? Pharmaceutical Research, 39(7), 1415-1455.