The effect of safranal loaded mucoadhesive nanoemulsion on oxidative stress markers in cerebral ischemia

Antioxidants, with reported neuroprotective activity, encounter free radical induced neural damage leading to reduced risk of cerebral ischemia-reperfusion (IR) injury. Safranal, an antioxidant drug with potential role in the amelioration of cerebral ischemia, endures low solubility and poor absorption property thus resulting a low serum and tissue bioavailability. This research aims to prepare nanoemulsion with the concept; to increase the bioavailability in order to reduce oxidative stress-induced brain injury as well as to evaluate the brain-drug targeting following non-invasive nasal route administration in middle cerebral artery occlusion (MCAO) animal model. Titration method was used to prepare safranal mucoadhesive nanoemulsion (SMNE) followed by further characterization, i.e. entrapment efficiency, particles size, and zeta potential study. Optimized SMNE showed; mean globule size of 89.64nm (+/- 9.12), zeta potential -11.39mV (+/- 1.32), drug content 98.47% (+/- 1.01), and viscosity of 124cp (+/- 14). Rats were subjected to 2h of MCAO, successively followed by a 22h reperfusion, after which the grip strength, locomotor activity, and biochemical studies, i.e. glutathione reductase (GR), glutathione peroxidase, lipid peroxidation, catalase, and superoxide dismutase were studied as assessment tool for effective treatment in brain. SMNE administered i.n. (intranasal) in MCAO induced cerebral ischemia rats exhibited significant improvement in neurobehavioral (locomotor and grip strength) and antioxidant activity as well as histopathological studies. The toxicity studies performed at the end revealed safe nature of developed SMNE.