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

• Published in: International journal of pharmaceutics Vol. 602; p. 120604
• Main Authors: Salama, Alaa H., Salama, Abeer A.A., Elhabak, Mona
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2021
• Subjects: Chitosan nanoparticles; EAAT; Epilepsy; GABA; Gabapentin; Nanospray dryer; TPGS; Chitosan nanoparticles; Gabapentin; Nanospray dryer; Epilepsy; GABA; TPGS; EAAT
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2021.120604

[Display omitted] •Gabapentin loaded chitosan nanoparticles (107 nm) prepared using Nano Spray Dryer.•Intranasal Rhodamine labeled chitosan nanoparticles exhibited high brain uptake.•Nose-brain delivery of gabapentin overcomes poor oral bioavailability problem.•Intranasal spray dried optimized formulation showed promising seizure treatment. 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-α-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 μm 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 γ-aminobutyric acid (GABA) brain contents. Nanospray dried GBP-loaded chitosan NPs reduced seizure score, neuroinflammation; TNF-α and TGF-β, elevated EAAT 2 and GABA as well as decreased degeneration in pyramidal neurons compared to marketed product Conventin® capsules. Thus, it can be concluded from the aforementioned data that nanospray dried GBP-loaded chitosan NPs could comprise an appropriate treatment of epilepsy.