Objectives: It has previously been shown that the peptide (34Pro,35Phe)CGRP27-37 is a potent calcitonin gene-related peptide, CGRP receptor antagonist, and in this project we aimed to improve the antagonist potency through the structural modification of truncated C-terminal CGRP peptides.
Methods: Six peptide analogues were synthesized and the anti-CGRP activity confirmed using both in vitro and in vivo studies.
Key findings: A 10 amino acid-containing peptide VPTDVGPFAF-NH2 (P006) was identified as a key candidate to take forward for in vivo evaluation, where it was shown to be an effective antagonist after intraperitoneal injection into mice. P006 was formulated as a preparation suitable for nasal administration by spray drying with chitosan to form mucoadhesive microcarriers (9.55 ± 0.91 mm diameter) and a loading of 0.2 mg peptide per 20 mg dose.
Conclusions: The project has demonstrated the potential of these novel small peptide CGRP antagonists, to undergo future preclinical evaluation as anti-migraine therapeutics.
Keywords: CGRP antagonist; chitosan microparticles; migraine; nasal delivery; peptide.
© The Author(s) 2023. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society.