Stem Cell-Based Human Blood-Brain Barrier Models for Drug Discovery and Delivery.

Area of Science:

• Neuroscience
• Pharmacology
• Biotechnology

Background:

• Evaluating novel neuropharmaceuticals necessitates understanding blood-brain barrier (BBB) permeability and toxicity.
• Significant interspecies variations exist in BBB composition, notably in P-glycoprotein (P-gp) and claudin expression.
• Functional differences in P-gp substrate pharmacokinetics between humans and rodents impact drug development.

Purpose of the Study:

• To review interspecies differences in the blood-brain barrier (BBB).
• To discuss recent advancements in developing human BBB models.
• To explore the application of these models in drug discovery and delivery.

Main Methods:

• Literature review of species-specific BBB characteristics.
• Analysis of recent research on human BBB model generation.
• Examination of studies utilizing BBB models for drug screening.

Main Results:

• Key BBB differences among species involve transporters like P-glycoprotein and structural proteins such as claudins.
• Human BBB models offer a promising platform for initial drug screening.
• Utilizing human BBB models can potentially decrease drug development costs and reduce clinical trial attrition.

Conclusions:

• Interspecies BBB variability, especially in transporter expression, is a critical consideration for neuropharmaceuticals.
• Human BBB models are valuable tools for early-stage drug evaluation.
• Implementing human BBB models in preclinical workflows can enhance the efficiency and success rate of drug development.