Strategies for Transcytosis-Based Delivery across the Blood-Brain Barrier

Area of Science:

• Neuroscience
• Biotechnology
• Pharmacology

Background:

• Transcytosis across brain microvascular endothelial cells (BMEC) is key for delivering biologics and nanocarriers to the brain.
• The efficiency of brain uptake is influenced by the complex interactions between therapeutic properties and BMEC transport mechanisms.

Purpose of the Study:

• To propose a framework for optimizing the delivery of large therapeutics across the blood-brain barrier.
• To elucidate the interplay between therapeutics and BMEC surface/intracellular targets to enhance brain delivery.

Main Methods:

• The study proposes a conceptual framework analyzing three key components of drug delivery: BMEC surface availability, transcytosis, and bloodstream availability.
• It reviews how modulating interactions with BMEC surface and intracellular proteins can improve transport.

Main Results:

• The framework highlights that optimizing interactions can minimize unproductive trafficking and entrapment, thereby maximizing transcytosis.
• Strategies to increase bloodstream availability of therapeutics are suggested.

Conclusions:

• Balancing adjustments in therapeutic-BMEC interactions and bloodstream availability is crucial for improving overall blood-brain barrier transport.
• This approach provides a roadmap for enhancing the delivery of large therapeutics to the brain.