Brain Targeting by Intranasal Drug Delivery: Effect of Different Formulations of the Biflavone "Cupressuflavone" from Juniperus sabina L. on the Motor Activity of Rats.

Abstract

The polar fractions of the Juniperus species are rich in bioflavonoid contents. Phytochemical study of the polar fraction of Juniperus sabina aerial parts resulted in the isolation of cupressuflavone (CPF) as the major component in addition to another two bioflavonoids, amentoflavone and robustaflavone. Biflavonoids have various biological activities, such as antioxidant, anti-inflammatory, antibacterial, antiviral, hypoglycemic, neuroprotective, and antipsychotic effects. Previous studies have shown that the metabolism and elimination of biflavonoids in rats are fast, and their oral bioavailability is very low. One of the methods to improve the bioavailability of drugs is to alter the route of administration. Recently, nose-to-brain drug delivery has emerged as a reliable method to bypass the blood-brain barrier and treat neurological disorders. To find the most effective CPF formulation for reaching the brain, three different CPF formulations (A, B and C) were prepared as self-emulsifying drug delivery systems (SEDDS). The formulations were administered via the intranasal (IN) route and their effect on the spontaneous motor activity in addition to motor coordination and balance of rats was observed using the activity cage and rotarod, respectively. Moreover, pharmacokinetic investigation was used to determine the blood concentrations of the best formulation after 12 h. of the IN dose. The results showed that formulations B and C, but not A, decreased the locomotor activity and balance of rats. Formula C at IN dose of 5 mg/kg expressed the strongest effect on the tested animals.