Thermosensitive transniosomal in situ gel of hesperetin for intranasal administration: Novel approach for Parkinson’s therapy

The present study aims to formulate and evaluate a thermosensitive transniosomal in situ gel of hesperetin (HST-TN) for intranasal delivery to improve its therapeutic efficacy in Parkinson's disease management. HST-TN was prepared via thin film hydration and optimized using Box-Behnken design. The optimized formulation (Opt-HST-TN) was incorporated into a Poloxamer 407-based in situ gel for sustained drug release. Opt-HST-TN exhibited vesicles size (100.50 ± 4.60 nm), PDI (0.247 ± 0.01), zeta potential (-32.50 ± 5.4 mV), and entrapment efficiency (91.71 ± 2.28%). The in vitro drug release study demonstrated 77.58 ± 0.15% drug release from Opt-HST-TN in 24 h. Ex vivo permeation finding showed 82.24% penetration and a flux of 5.16 µg/cm2/h, approximately 2-fold higher than HST suspension. Confocal laser scanning microscopy confirmed that Opt-HST-TN containing Rhodamine B showed superior mucosal penetration (30 µm) than Rhodamine B hydroethanolic solution (20 µm). Further, nasal toxicity studies have confirmed the Opt-HST-TTN's non-irritant nature. The prepared formulation significantly improved motor coordination, grip strength, and locomotor activity in haloperidol-induced Parkinson's disease Wistar rats after intranasal administration. These findings suggest that HST-loaded thermosensitive transniosomal in situ gel is an encouraging intranasal drug delivery system for PD, offering enhanced bioavailability, nasal permeability, and therapeutic efficacy.