Formulation of a novel diosgenin-loaded nanoemulsion and its evaluation for improved brain bioavailability in the management of cerebral ischemia

Objective Stroke is one of the leading causes of death globally, causing irreversible CNS damage due to free radical generation. Diosgenin shows promise against cerebral ischemia but suffers from poor solubility and absorption. This study developed an oral diosgenin-loaded nanoemulsion to enhance brain bioavailability and a validated LC-MS/MS method was developed to measure diosgenin levels in the brains of ischemic rats’ post-treatment. Methods To enable diosgenin (DGN) to cross the blood–brain barrier for ischemic brain treatment, a diosgenin-loaded nanoemulsion (DGN-NE) was developed using the Box–Behnken design and ultrasonication techniques. The formulation was optimized and evaluated for brain bioavailability. Neurobehavioral, biochemical, and histopathological assessments were accomplished to determine the medicinal efficacy of DGN-NE in treating cerebral ischemia. Results The optimized DGN-NE had a globule size of 195.2 ± 19.82 nm, 0.054 ± 0.003 PDI, −8.15 ± 0.41 mV zeta potential, and 98.01 ± 1.03 % transmittance. Its low viscosity favored oral delivery, and stability studies confirmed consistent physicochemical properties. DGN exhibited an initial burst release, followed by a sustained release pattern, resulting in a total permeation of 82.64 ± 6.11 %. LC-MS/MS analysis showed 0.842 min RT and 415.3/271.3 m/z , with a linearity range of 0.5–1200 ng/mL. Accuracy ranged from 96.62 to 99.21 %, and CV from 1.80 to 3.62 %. Oral DGN-NE significantly improved pharmacokinetic parameters (AUC_0-24, Cmax; p < 0.001) and showed strong neuroprotective effects in MCAO-induced ischemic rats, supported by biochemical, neurobehavioral, and histopathological evaluations. Conclusion The study demonstrated that the DGN-loaded nanoemulsion (DGN-NE) significantly enhanced brain bioavailability of diosgenin following oral administration in rats. This improved delivery contributed to notable neuroprotective effects in the treatment of cerebral ischemia, even at a low dose of diosgenin.