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Nose to Brain Delivery of Thermosensitive Hydrogel System Containing Riluzole Nanosuspension: Design, Physicochemical Characterization and Antidepressant Efficacy Publisher



S Taymouri SOMAYEH ; F Kazemi FATEMEH ; A Mesripour AZADEH ; A Mostafavi ABOLFAZEL
Authors

Source: Journal of Dispersion Science and Technology Published:2025


Abstract

The objective of this study was to fabricate a chitosan based thermosensitive in situ gel containing riluzole nanosuspension (RLZ-NS) for intranasal drug delivery to the brain. Accordingly, RLZ-NS was produced using anti-solvent crystallization method and optimized based on saturation solubility (Cs), particle size (PS), polydispersity index (PDI), zeta potential (ZP), and dissolution efficiency percentage after 90 minutes (DE90 min%). An I-optimal response surface methodology design was then used to evaluate the impact of the anti-solvent/solvent volume ratio, polymer content and polymer type on these variables. The optimal formulation was then incorporated into a thermosensitive chitosan–β-glycerophosphate hydrogel (RLZ-NS-Hydrogel) and subjected to various evaluations including pH, gelation time, in vitro release, and histopathological tests. The therapeutic efficacy of the optimal RLZ-NS-Hydrogel was tested using the behavioral models of depression in mice. The optimal formulation exhibited a Cs of 683.64 ± 31.14 µg/ml, a PS of 398.70 ± 10.56 nm, a PDI of 0.38 ± 0.01, a ZP of −20.35 ± 2.33 mV, and DE90 min% of 69.23 ± 0.97%. Scanning electron microscopy also revealed that RLZ-NS had a spherical shape. Further, the histopathological effects in sheep nasal mucosa showed that RLZ-NS-Hydrogel had no significant impact on the microscopic structure of mucosa and could be safe for nasal administration. Intranasal administration of RLZ-NS-Hydrogel also produced an antidepressant-like effect comparable to intraperitoneal RLZ in mice, and it was increased, as compared to oral RLZ and intranasal RLZ-Hydrogel. In conclusion, RLZ-NS-Hydrogel showed a potential for nose to brain delivery in treatment of depression. © 2025 Elsevier B.V., All rights reserved.
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