Single step nanospray drying preparation technique of gabapentin-loaded nanoparticles-mediated brain delivery for effective treatment of PTZ-induced seizures

In the present study, gabapentin (GBP)-loaded chitosan nanosized particles were fabricated applying the nanospray drying technique. Different preparation parameters (spray mesh diameter, chitosan concentration and presence of D-alpha-Tocopherol polyethylene glycol 1000 succinate (TPGS) were studied while fixing other parameters (spraying rate, inlet temperature and gas flow rate). An optimized formulation with a particle size 107 +/- 13 nm was obtained upon spraying 0.1% (w/v) chitosan solution containing 0.05% (w/v) of TPGS utilizing the small nozzle (4 um spray mesh hole size). Drug entrapment efficiency and yield were as high as 95% and 83%, respectively. A 98.1 +/- 6.1% (w/w) cumulative drug release was recorded after 2 h. Confocal laser scanning microscopy showed higher fluorescent dye penetration into brain tissue following intranasal administration of Rhodamine B labeled spray dried chitosan nanoparticles (NPs) as compared to Rhodamine B solution. Pentylenetetrazole (PTZ) was used to induce convulsions in rats through elevating seizure stages, releasing neuroinflammatory mediators and reducing excitatory amino acid transporter 2 (EAAT 2) and gamma-aminobutyric acid (GABA) brain contents. Nanospray dried GBP-loaded chitosan NPs reduced seizure score, neuroinflammation; TNF-alpha and TGF-beta, elevated EAAT 2 and GABA as well as decreased degeneration in pyramidal neurons compared to marketed product Conventin (R) capsules. Thus, it can be concluded from the aforementioned data that nanospray dried GBP-loaded chitosan NPs could comprise an appropriate treatment of epilepsy.

Automated summary

Gabapentin-loaded chitosan nanosized particles were successfully prepared using nanospray drying technique, showing promising drug release properties and neuroprotective effects in the treatment of epilepsy.