| Summary: | Background: 6-Gingerol (GRL), as an antioxidant nonvolatile, phenolic component of ginger showed a capable function in the treatment of cerebral ischemia but their poor solubility and low absorption gives low bioavailability in the brain. Purpose: The main purpose of proposed study is to develop a novel GRL-loaded-nanoemulsion (GRL-NE) and converted to mucoadhesive nanoemulsion (GRL-MNE) for intranasal delivery to brain. Methods: Aqueous microtitration method was used to formulate GRL-NE using Lauroglycol 90, Tween 80 and PEG-400 as the oil phase, surfactant, and co-surfactant with the help of CS converted into mucoadhesive-GRL-MNE was evaluated for morphology, physicochemically, stability in terms of thermodynamic, release (in vitro), mucoadhesive potency, and nasal permeation (ex-vivo) to enhance brain bioavailability and other PK-parameters. Results: Opt-GRL-MNE showed mean globule-size (94.89 ± 2.61 nm), PDI (0.129 ± 0.091) and +ve ZP (1.892 ± 0.068 mV). Excellent mucoadhesive-nature of GRL-MNE as compared with GRL-S was found with their retention time (1.27 min) and m/z: 295.3764/137.0763 for GRL, alongwith a retention time (1.12 min) and m/z: 294.3126/137.1802 for Nonivamide (internal standard; IS). 1.0–1000.0 ng/mL linear range, % inter-and-intraday accuracy (94.12–98.97%) and CV (2.06–4.04%) were calculated. A highly significant (p < 0.001) results were found for enhanced Cmax with their area under curve (AUC)0–24 of based on i.n. and i.v. treated-groups of rats. Moreover, significantly results were observed for neurobehavioral and biochemical assessment with their histopathological assessment and reduction of infarction-volume in MCAO-induced brain-ischemic model after the delivered GRL-MNE via intranasal route. Conclusion: GRL-MNE showed a significant (p < 0.001) role for the improvement of brain-bioavailability in the treatment of cerebral ischemia with improving their neuroprotection at very low-dose of GRL. © 2020 Elsevier B.V.
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