Thermosensitive In Situ Nasal Gel Incorporating Chitosan Nanoparticles of Zolmitriptan for Migraine Management: Formulation Strategies, Optimization, and Characterization— A Review

Abstract

Migraine is a prevalent neurovascular disorder characterized by recurrent attacks of moderate to severe headache, frequently associated with nausea, vomiting, photophobia, and phonophobia, leading to substantial impairment in quality of life and socioeconomic burden. Conventional oral therapy with Zolmitriptan, a selective serotonin 5-HT1B/1D receptor agonist, is clinically effective for acute migraine management but suffers from limitations including hepatic first-pass metabolism, delayed gastric emptying during migraine episodes, variable bioavailability, and reduced patient compliance in nausea-associated attacks. Intranasal delivery has emerged as a promising non-invasive strategy capable of providing rapid systemic absorption and direct noseto-brain transport, thereby improving onset of action and therapeutic effectiveness. Recent advances in nanotechnology and intelligent polymeric delivery systems have significantly expanded the scope o nasal formulations for antimigraine therapy. Chitosan nanoparticles have attracted considerable attention because of their mucoadhesive properties, biocompatibility, permeation-enhancing ability, and capacity for controlled drug release. Furthermore, incorporation of nanoparticulate systems into thermosensitive in situ gels offers additional advantages, including prolonged nasal residence time, temperaturetriggered gelation, enhanced mucosal contact, and sustained drug release. The synergistic integration of chitosan nanoparticles with thermoreversible gel systems represents a highly promising platform for targeted intranasal delivery of Zolmitriptan. This review critically discusses the pathophysiological basis of migraine therapy, pharmaceutical limitations of conventional Zolmitriptan formulations, scientific rationale for nasal drug delivery, formulation strategies involving chitosan nanoparticles, thermosensitive gel systems, optimization methodologies, characterization parameters, and recent progress in translational intranasal antimigraine drug delivery research. Special emphasis is placed on formulation design principles that may improve bioavailability, brain targeting efficiency, and patient therapeutic outcomes.