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Review
. 2023 Jul 28;15(8):2032.
doi: 10.3390/pharmaceutics15082032.

The Potential of the Nose-to-Brain Delivery of PACAP for the Treatment of Neuronal Disease

Asma Cherait  1   2   3 , William A Banks  4   5 , David Vaudry  1   6
Affiliations
Review

The Potential of the Nose-to-Brain Delivery of PACAP for the Treatment of Neuronal Disease

Asma Cherait et al. Pharmaceutics. .

Abstract

Research on the neuroprotective effect of pituitary adenylate cyclase-activating polypeptide (PACAP) and its use as a therapeutic agent has grown over the past 30 years. Both in vitro and in vivo experiments have shown that PACAP exerts a strong neuroprotective effect in many central and peripheral neuronal diseases. Various delivery routes have been employed from intravenous (IV) injections to intracerebroventricular (ICV) administration, leading either to systemic or topical delivery of the peptide. Over the last decade, a growing interest in the use of intranasal (IN) administration of PACAP and other therapeutic agents has emerged as an alternative delivery route to target the brain. The aim of this review is to summarize the findings on the neuroprotective effect of PACAP and to discuss how the IN administration of PACAP could contribute to target the effects of this pleiotropic peptide.

Keywords: apoptosis; cerebral plasticity; inflammation; intranasal delivery route; neuronal diseases; neuroprotection; pituitary adenylate cyclase-activating polypeptide; redox state.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Multi-neuroprotective mechanisms of PACAP administrated intranasally in neurodegenerative disease (ND). The figure was created with BioRender.com and Microsoft PowerPoint 2021.
Figure 2
Figure 2
Summary of the advantages using nose-to-brain PACAP administration in the clinic. The figure was created using BioRender.com and Microsoft PowerPoint 2021.
Figure 3
Figure 3
Summary of the difficulties associated with the use of nose-to-brain (NtB) PACAP administration in clinic. The figure was created using Microsoft PowerPoint 2021.
Figure 4
Figure 4
Arterial blood pressure measurement (mmHg) before and after nose-to-brain (NtB) delivery of PACAP (n = 5) and NaCl (n = 4) in mice. All animals were treated with a single NtB administration of 10 µL of PACAP (1 µg/µL) or Nacl (0.9%). The figure was created using GraphPad Prism 6. Statistical analysis of the results revealed no significant differences.
See this image and copyright information in PMC

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