Ischemic brain treated with 6-gingerol loaded mucoadhesive nanoemulsion via intranasal delivery and their comparative pharmacokinetic effect in brain

• Published in: Journal of drug delivery science and technology Vol. 61; p. 102130
• Main Authors: Ahmad, Niyaz, Ahmad, Rizwan, Amir, Mohd, Alam, Md Aftab, Almakhamel, Mortaja Zaki, Ali, Abuzer, Ahmad, Ayaz, Ashraf, Kamran
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.02.2021
• Subjects: 6-Gingerol; Brain pharmacokinetics and pharmacodynamics; MCAO-Cerebral ischemia; Mucoadhesive-nanoemulsion; UHPLC-MS/MS; Mucoadhesive-nanoemulsion; MCAO-Cerebral ischemia; Brain pharmacokinetics and pharmacodynamics; 6-Gingerol; UHPLC-MS/MS
• ISSN: 1773-2247
• DOI: 10.1016/j.jddst.2020.102130

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. 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. 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. 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. 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. [Display omitted]