Designing supramolecular therapies to cross the blood-brain barrier
A new Northwestern Medicine study has uncovered key molecular design principles that could help supramolecular therapeutics cross the blood-brain barrier, a major challenge for this novel approach to treating neurological disorders.
A Northwestern Medicine study has unlocked critical design principles for supramolecular therapies targeting the blood-brain barrier, a major hurdle for this emerging field of treatment for neurological disorders. The research, published in ACS Nano, examined how slight alterations in peptide amphiphile structures influence their ability to pass through brain endothelial cells and the blood-brain barrier.
The findings offer a blueprint for developing new therapies to reach the brain, potentially treating conditions like stroke, Alzheimer's disease, and Parkinson's disease. Samuel Stupp, the senior author and a distinguished professor, explained that while the blood-brain barrier protects the central nervous system, it also blocks most drugs from reaching their targets.
The team studied peptide amphiphiles with varying lipid tail lengths, discovering that longer tails created more stable nanostructures but hindered cell penetration, while shorter tails enabled easier passage but resulted in trapped structures within cells. Intriguingly, the nanostructures could disassemble during transport and reassemble post-exit, retaining functionality.
Stupp emphasized the need for a balance between stability and adaptability in supramolecular assemblies to ensure successful brain delivery. The study builds on previous work demonstrating the stroke treatment potential of supramolecular therapeutics and opens avenues for various administration routes beyond intravenous delivery.
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