Nanofiber-Based Delivery of Therapeutic Peptides to the Brain
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- 作者：Mariarosa Mazza ; Rebecca Notman ; Jamshed Anwar ; Alison Rodger ; Matthew Hicks ; Gary Parkinson ; Dave McCarthy ; Tina Daviter ; Julian Moger ; Natalie Garrett ; Tania Mead ; Michael Briggs ; Andreas G. Sch盲tzlein ; Ijeoma F. Uchegbu
- 刊名：ACS Nano
- 出版年：2013
- 出版时间：February 26, 2013
- 年：2013
- 卷：7
- 期：2
- 页码：1016-1026
- 全文大小：674K
- 年卷期：v.7,no.2(February 26, 2013)
- ISSN：1936-086X
文摘
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.