期刊
ACS NANO
卷 7, 期 2, 页码 1016-1026出版社
AMER CHEMICAL SOC
DOI: 10.1021/nn305193d
关键词
peptide brain delivery; blood-brain barrier; dalargin; palmitoyl dalargin; nanofibers; self-assembly
类别
资金
- The School of Pharmacy
- Advantage West Midlands
- Higher Education Funding Council for England
- BBRSC [BB/F011199/1]
- Biotechnology and Biological Sciences Research Council [BB/F011199/1] Funding Source: researchfish
- Engineering and Physical Sciences Research Council [EP/K502339/1, EP/G061564/1, EP/G061483/1, EP/K502340/1] Funding Source: researchfish
- BBSRC [BB/F011199/1] Funding Source: UKRI
- EPSRC [EP/K502340/1, EP/G061564/1, EP/K502339/1, EP/G061483/1] Funding Source: UKRI
The delivery of therapeutic peptides and proteins to the central nervous system is the biggest challenge when developing effective neuropharmaceuticals. The central issue is that the blood-brain barrier is impermeable to most molecules. Here we demonstrate the concept of employing an amphiphilic derivative of a peptide to deliver the peptide into the brain. The key to success is that the amphiphilic peptide should by design self-assemble into nanofibers wherein the active peptide epitope is tightly wrapped around the nanofiber core. The nanofiber form appears to protect the amphiphilic peptide from degradation while in the plasma, and the amphiphilic nature of the peptide promotes its transport across the blood-brain barrier. Therapeutic brain levels of the amphiphilic peptide are achieved with this strategy, compared with the absence of detectable peptide in the brain and the consequent lack of a therapeutic response when the underivatized peptide is administered.
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