Nasal In situ Gel of Zolmitriptan Loaded GMO Nanoparticles for Effective Migraine Treatment: In Vitro and In Vivo Assessment
The present work focused on formulating a glyceryl monooleate (GMO) based nanoparticulate system of zolmitriptan (ZMT) tailored for intranasal delivery to enhance its brain-targeting potential in migraine treatment. ZMT loaded GMO nanoparticles (ZMT-GMO-NPs) were produced via the thin-film hydration technique. A Box–Behnken statistical design, aligned with the principles of Quality by Design (QbD), was employed to investigate the influence of key formulation parameters on essential characteristics such as particle size (PS), zeta potential (ZP), and entrapment efficiency (EE%). The finalized formulation exhibited an average particle size of 150±0.6 nm, a polydispersity index (PDI) of 0.302±0.001, a zeta potential of −20.8±0.2 mV, and a notable entrapment efficiency of 83.3±0.4%. Compatibility of the excipients and the amorphous nature of the encapsulated drug were validated through Fourier-transform infrared spectroscopy and X-ray diffraction analyses. The optimized nanoparticles were further incorporated into a thermosensitive nasal in situ gel (NIG). In vitro release experiments demonstrated a sustained ZMT release profile from the GMO-NPs@NIG system (71±0.4%) compared to the immediate release observed with the plain ZMT-Solution (91.2±0.8%). Ex vivo studies using sheep nasal mucosa demonstrated enhanced permeability of ZMT from the GMO-NPs@NIG system. In vivo brain uptake studies in mice revealed significantly higher brain accumulation of ZMT with intranasal GMO-NPs@NIG than with oral ZMT solutions. Pharmacokinetic and pharmacodynamic evaluations confirmed improved brain targeting, enhanced bioavailability, and greater therapeutic efficacy. In conclusion, this intranasal ZMT-GMO-NP@NIG formulation offers a promising strategy for effective migraine management through targeted brain delivery.
The present work focused on formulating a glyceryl monooleate (GMO) based nanoparticulate system of zolmitriptan (ZMT) tailored for intranasal delivery to enhance its brain-targeting potential in…
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