Scopus
Intranasal hybrid nanoparticles encapsulating rizatriptan enhance antimigraine efficacy in an optogenetic spreading depression model
International Journal of Pharmaceutics · Nisan 2026
Makale Bilgileri
DergiInternational Journal of Pharmaceutics
Yayın TarihiNisan 2026
Cilt / Sayfa694
Scopus ID2-s2.0-105032463162
Özet
Cortical spreading depression (SD) is the likely cause of migraine aura and a putative headache trigger. Migraine treatments, including triptans and calcitonin gene related peptide (CGRP) receptor antagonists, are limited by poor bioavailability. This study evaluates whether intranasally administered poly lactic co-glycolic acid (PLGA) based hybrid nanoparticles (HNPs) encapsulating rizatriptan (RZT) could provide sustained drug release, enhance brain delivery, and improve therapeutic efficacy against periorbital allodynia triggered by optogenetic SD in mice. CGRP<inf>8-37</inf> was conjugated to the nanoparticle surface (HNP-CGRP<inf>8-37</inf>) and RZT encapsulated whitin HNPs (HNP-RZT). were intranasally administered alone or in combination and compared with intraperitoneal CGRP<inf>8-37</inf> and RZT. Formulations were characterized for particle size, zeta potential, and polydispersity index, and assessed for in vitro drug release, cytotoxicity, and in vivo brain RZT concentrations. In the acute SD model, periorbital allodynia was evaluated 1 h after a single SD. In the repeated SD paradigm, seven SDs were induced every other day, and periorbital thresholds were assessed up to 6 days after the final SD. HNPs exhibited uniform particle size (<200 nm), positive zeta potential, and low polydispersity. RZT release from HNP-RZT was sustained in vitro. Intranasal HNP-RZT demonstrated prolonged brain RZT retention compared with intraperitoneal RZT. In the acute SD model, HNP-RZT did not reach statistical significance (p = 0.065), whereas intraperitoneal RZT significantly increased periorbital thresholds. In contrast, in the repeated SD model, HNP-RZT demonstrated delayed but persistent suppression of allodynia compared with intraperitoneal RZT. These findings support the potential of intranasal nanoparticle-based delivery to prolong central exposure of RZT and enhance therapeutic durability in chronic SD conditions.
Yazarlar (9)
1
Melih Zeki Kaya
ORCID: 0000-0002-2874-6037
2
Yakup Gultekin
3
Mustafa Celebier
4
Murat Soyseven
ORCID: 0000-0002-6433-2392
5
İmran Vural
6
Levent Öner
ORCID: 0000-0002-6510-7680
7
Cenk Ayata
8
Sibel Bozdag Pehlivan
9
Andrea M. Harriott
ORCID: 0000-0003-0417-7586
Anahtar Kelimeler
CGRP8-37
Hybrid nanoparticle
Migraine
Optogenetic cortical spreading depression
Periorbital allodynia
Rizatriptan
Kurumlar
Anadolu Üniversitesi
Eskisehir Turkey
Hacettepe Üniversitesi
Ankara Turkey
Massachusetts General Hospital
Boston United States