Brain-targeted nasal chrysin microemulsion for reducing oxidative stress in Parkinson's disease: Pharmacodynamic, biochemical evaluation and brain distribution studies

Abstract

Chrysin, a flavone reported to treat Parkinson's, has limited oral bioavailability due to poor solubility and extensive pre-systemic metabolism. Therefore, a chrysin microemulsion (Chy-ME) was developed to improve bioavailability and brain targeting for treating Parkinson's disease via the nasal route. Chy-ME was prepared using the phase titration method and characterized for physicochemical parameters, nasociliotoxicity, and anti-Parkinson activities in a rotenone-induced experimental rat model. Chy-ME showed spherical globules with a size of 365.03 nm ± 6.8, a PDI of 0.107 ± 0.0316 and a zeta potential of −24.86 mV ± 2.286. It was non-irritant to the nasal mucosa and had in vitro and ex vivo drug release of 90.52 % and 68.67 %, respectively at 24 h. The in vivo study showed significantly improved locomotor activity and catalepsy score in the Chy-ME treated group than in oral or nasal chrysin suspension groups in rats. Chy-ME treatment showed elevated dopamine levels than the other two groups. Also, enhanced oxidative stress markers, i.e., SOD, GSH, and catalase levels, indicated the antioxidant potential of Chy-ME linked with preventing neuronal damage in Parkinson's. The maximum chrysin amount was estimated in the Chy-ME group (8.3212 ± 1.8125 μg/mL) than in oral (4.1364 ± 1.1095 μg/mL) or nasal (5.0879 ± 0.0058 μg/mL) suspension groups in the brain distribution study. In vivo studies revealed the brain-targeting potential of Chy-ME, evidenced by a substantial alleviation of Parkinson's symptoms, increased dopamine levels, improved oxidative stress markers and higher chrysin content in the brain. Therefore, nasal delivery of chrysin could overcome poor oral bioavailability and be explored for treating Parkinson-related symptoms as a brain-targeted approach.