Optimization of Ionic Liquid Based NLC for Nose-To-Brain Delivery of Tetrabenazine Hydrochloride

Nanostructured lipid carriers (NLCs) have been researched extensively for nose-to-brain drug delivery but are often constrained by low drug solubility, limited payload, and poor permeability. Herein, we have developed Hybrid NLCs (Liquid lipid replaced with bioionic liquid) to enhance drug solubility, permeability, payload, and nose-to-brain bioavailability of Tetrabenazine hydrochloride (TBZ), a BCS-class IV drug. The formulation and optimization of the Hybrid-NLCs was carried out using a central composite design, followed by loading into an in-situ gel. The optimized TBZ Hybrid-NLCs demonstrated a particle size of 149.84 ± 0.73 nm, PDI 0.33 ± 0.01, zeta potential -38.96 ± 0.09 mV, and % Entrapment efficiency 97.65 ± 0.70%. The % Drug loading of TBZ in Hybrid-NLCs was significantly higher (34.4 ± 0.98%) compared to 28.2 ± 0.54% in conventional or Plain NLCs, reflecting superior drug-loading (p < 0.05). Comparative in-vitro and ex-vivo drug release studies revealed improved TBZ release (74.22 ± 0.20% in-vitro, and 74.73 ± 0.64% ex-vivo) from Hybrid-NLCs, compared to the Plain-NLCs (66.44 ± 0.21% in-vitro and 61.18 ± 0.39% ex-vivo). Intranasal administration of TBZ-loaded-Hybrid-NLC gels in Wistar rats showed C_max 7.87 ± 0.80 µg/ml and T_max 5-6 h in brain tissue, outperforming (Plain-NLC), achieving C_max 6.32 ± 0.30 µg/ml and a similar T_max. Conclusively, the nose-to-brain delivery of TBZ-loaded Hybrid-NLCs gel significantly enhanced TBZ bioavailability to the brain, 1.51-fold over Plain-NLCs gel. Findings underscored Hybrid-NLCs as a promising non-invasive strategy for enhancing the bioavailability of BCS class IV drugs via nose to brain delivery, prospective in the treatment of neurological diseases/disorders.