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The Blood-brain Barrier

The Blood-brain Barrier

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Updated: Jan 10, 2026

Setting-up an In Vitro Model of Rat Blood-brain Barrier BBB: A Focus on BBB Impermeability and Receptor-mediated Transport

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Published on: June 28, 2014

A Chemically Engineered Macrocyclic Peptide Shuttle Overcomes Blood-Brain Barrier in Aging Brain.

Licong Peng^1,2, Qihang Li¹, Zhizhi Li³

¹Institute of Biomedical Engineering, College of Medicine, Southwest Jiaotong University, Chengdu, Sichuan, 610031, P. R. China.

Angewandte Chemie (International Ed. in English)

|November 25, 2025

Summary

Scientists developed a novel macrocycle peptide shuttle to overcome blood-brain barrier (BBB) challenges in aging brains. This new strategy enhances drug delivery for age-related neurodegenerative diseases.

Keywords:

Aging brain Blood‐brain barrier Caveolae‐mediated transcytosis Macrocyclic peptides Neurodegenerative diseases

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Last Updated: Jan 10, 2026

Setting-up an In Vitro Model of Rat Blood-brain Barrier BBB: A Focus on BBB Impermeability and Receptor-mediated Transport

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Area of Science:

Neuroscience
Biotechnology
Drug Delivery

Background:

The blood-brain barrier (BBB) restricts therapeutic entry into the central nervous system.
Receptor-mediated transcytosis (RMT) is effective for BBB drug delivery but declines with age.
Age-related decline in BBB receptor function necessitates new therapeutic delivery strategies.

Purpose of the Study:

To develop an age-adapted strategy for enhanced therapeutic delivery across the BBB.
To discover a novel neuron-targeting shuttle that utilizes age-potentiated transcytosis pathways.
To create a safe and efficient platform for treating age-related neurological disorders.

Main Methods:

Engineered a macrocyclic peptide shuttle with specific cross-linking architectures and tuned lipophilicity.
Investigated caveolae-mediated transcytosis, a pathway enhanced in aged brain endothelial cells.
Evaluated shuttle efficacy and biosafety in aged murine models.

Main Results:

The perfluoroalkane-tethered macrocycle demonstrated superior BBB traversal efficiency compared to existing RMT shuttles.
The shuttle successfully triggered caveolae-mediated transcytosis, bypassing age-dependent receptor downregulation.
The macrocycle architecture achieved an optimal balance between BBB permeability and low cytotoxicity.

Conclusions:

The developed macrocycle peptide shuttle platform offers efficient BBB traversal and neuron-targeting in the aging brain.
This approach shows significant promise for therapeutic delivery in age-related neurodegenerative diseases.
The study highlights the potential of targeting age-enhanced pathways for improved drug delivery.