Investigating the Potential of Brain Targeting of Edaravone through Transferosomes Embedded Intranasal Drug Delivery System: In-vitro and In- vivo Characterization

Neurodegeneration is the leading cause for the development of brain-related disorders. A high level of oxidative stress is one of the reasons for the neurodegeneration. Edaravone (EDR) is a potent antioxidant that belongs to BCS class VI. Owing to low solubility and permeability and substrate of p-GP, EDR suffers from poor bioavailability. This research focused on the development of transferosomes as a potential delivery carrier system of EDR to target the brain. Transferosomes, being flexible vesicular formulations, demonstrated greater drug entrapment capacity. The EDR-entrapped transferosomes were incorporated into in-situ gel comprised of gellan gum for administration through nasal mucosa. The prepared nasal formulation showed less than 50 sec gelation time with 60% of in-vitro drug diffusion in one hour. The nasal permeation study on goat nasal mucosa depicted 55% of drug permeation in 22.184cm2/60 minutes. Results of histopathology study also confirmed its safety in nasal mucosa. A brain-targeting study was performed in comparison to marketed injections, which showed better drug distribution. The obtained Cmax and mean residence time were 61.975ng/ml and 267 minutes, respectively. These findings suggest the in-situ nasal gel formulation as an efficacious noninvasive method of administration of EDR for better patient suitability. This formulation can be further evaluated for clinical performance.