Transient Opening of the Blood-Brain Barrier by Vasoactive Peptides to Increase CNS Drug Delivery: Reality Versus Wishful Thinking?
Document Type
Article
Publication Date
1-31-2022
Publication Title
Curr Neuropharmacol
Keywords
washington; seattle; swedish neuro
Abstract
BACKGROUND: The blood-brain barrier inhibits the central nervous system penetration of 98% of small molecule drugs and virtually all biologic agents, which has limited progress in the treatment of neurologic disease. Vasoactive peptides have been shown in animal studies to transiently disrupt the blood-brain barrier and regadenoson is currently being studied in humans to determine if it can improve drug delivery to the brain. However, there are many other vasoactive peptides that could potentially be used for this purpose.
METHODS: We performed a review of the literature evaluating the physiologic effects of vasoactive peptides on the vasculature of the brain and systemic organs. To assess the likelihood that a vasoactive peptide might transiently disrupt the blood-brain barrier, we devised a four-tier classification system to organize the evidence available.
RESULTS: We identified 33 vasoactive peptides with potential blood-brain barrier permeability-altering properties. To date, none of these are shown to open the blood-brain barrier in humans. 12 vasoactive peptides increased blood-brain barrier permeability in rodents. The remaining 23 had favorable physiologic effects on blood vessels but lacked specific information on permeability changes to the blood-brain barrier.
CONCLUSION: Vasoactive peptides remain an understudied class of drugs with the potential to increase drug delivery and improve treatment in patients with brain tumors and other neurologic diseases. Dozens of vasoactive peptides have yet to be formally evaluated for this important clinical effect. This narrative review summarizes the available data on vasoactive peptides, highlighting agents that deserve further in vitro and in vivo investigations.
Clinical Institute
Neurosciences (Brain & Spine)
Department
Neurosciences
Department
Oncology
Department
Pharmacy
Recommended Citation
Smith-Cohn, Matthew A; Burley, Nicholas B; and Grossman, Stuart A, "Transient Opening of the Blood-Brain Barrier by Vasoactive Peptides to Increase CNS Drug Delivery: Reality Versus Wishful Thinking?" (2022). Articles, Abstracts, and Reports. 5839.
https://digitalcommons.providence.org/publications/5839
