Intranasal delivery of kaempferol via magnesomes for brain seizure treatment: Design, characterization, and biodistribution studies

Abstract

The current study aims to develop phospholipid magnesomes retaining the inherent neuroprotective activities of kaempferol as a proposed treatment approach for epilepsy. Magnesomes were prepared using varied amounts of phospholipid, magnesium sulfate and poloxamer 188, and evaluated on in-vitro and in-vivo levels. The prepared vesicles possessed nanosizes (112-625 nm), negative charges (-16 to -20 mV), and entrapment efficiency (80–96 %) with negligible changes in their colloidal properties after 3 months’ storage. Magnesomes showed sustained release of kaempferol as well as superior permeability relative to drug solution. Radiolabeling of kaempferol with iodine-131 was successfully performed using electrophilic substitution. The superior brain uptake of intranasally delivered ¹³¹I-kaempferol-magnesomes containing 3.13 µg/20µl of kaempferol compared to intravenous and intranasal solutions was demonstrated employing biodistribution and pharmacokinetic tests conducted using Swiss Albino male mice. Brain to blood ratio of the intranasally administered kaempferol was significantly higher compared to intravenous injection showing uptake of 9.9 ± 0.3 % injected dose per gram organ at the first 5 min ensuring a rapid onset of action. The drug targeting efficiency and nose to brain direct transport percentages of ¹³¹I- kaempferol-magnesomes were 215.0 and 87.0 %, respectively with relative bioavailability of 810.24 ± 119.1 %. Accordingly, intranasal kaempferol-magnesomes showed effectiveness in brain targeting and could be beneficial for managing epileptic seizures.