Understanding drug nanocarrier and blood-brain barrier interaction based on a microfluidic microphysiological model

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Neuroscience

Background:

• Blood-brain barrier (BBB) poses a significant challenge for drug delivery.
• Nanoparticles (NPs) are promising drug carriers, but their interaction with the BBB requires better understanding.
• Reliable in vitro BBB models are crucial for evaluating nanodrug efficacy and safety.

Purpose of the Study:

• To develop and validate a microfluidic microphysiological model for analyzing BBB homeostasis and nanoparticle (NP) penetration.
• To investigate the influence of NP size and surface modification on BBB penetration.
• To explore the role of the protein corona in NP-BBB interactions.

Main Methods:

• Development of a microfluidic microphysiological system mimicking the BBB.
• Assessment of nanoparticle (NP) penetration across the model.
• Analysis of BBB homeostasis and dysfunction.
• Characterization of the protein corona formed on NPs.
• Evaluation of the effect of PEGylation on protein absorption.

Main Results:

• Nanoparticle (NP) penetrability across the BBB model was dependent on size and surface modification.
• Transferrin-modified 13 nm gold nanoparticles (AuNPs) exhibited the highest BBB penetrability and caused the least BBB dysfunction.
• Bare 80 nm and 120 nm AuNPs showed lower penetrability and induced more BBB dysfunction.
• PEGylation reduced protein absorption on NPs.
• Specific proteins in the corona were found to facilitate NP penetration.

Conclusions:

• The developed microfluidic model is a powerful tool for studying drug nanocarrier-BBB interactions.
• Nanoparticle properties significantly influence BBB penetration and potential for dysfunction.
• Understanding protein corona formation is key to designing effective nanodrugs for brain delivery.