Brain-targeted Brivaracetam delivery using mannose-functionalized mesoporous silica nanoparticles for the treatment...

Surface-engineered mesoporous silica nanoparticles (MSN) as carrier system for controlled release of Brivaracetam (BVM) for targeted brain delivery in epilepsy were developed and evaluated. Modified sol-gel process employed to synthesize MSN using tetraethylorthosilicate (TEOS) as silica source and cetyltrimethylammonium bromide (CTAB) as structure-directing agent, followed by calcination. Surface functionalization was achieved by grafting aminopropyl triethoxysilane (APTES) to introduce amine groups. Surface modification was carried out by amination, followed by the conjugation of D-mannose. Physical adsorption method was used to incorporate BVM into MSN. In-vitro studies revealed that BVM solution released 96.11% of drug within 5 h, while MSN formulation extended release upto 98.13% over 24 h. 94.25% of the drug release was observed from mannose-conjugated amine MSN over 48 h, aligning with Korsmeyer-Peppas model. Maximal Electroshock seizures (MES) model used for In-vivo pharmacodynamic evaluation, indicated that untreated group experienced 16.25 ± 1.11 seizure episodes (absence of treatment). BVM loaded MSN treatment reduced to 13.25 ± 1.11 episodes (69.63% antiepileptic effect), while mannose-conjugated BVM-loaded MSN group further decreased to 12.5 ± 1.32 episodes (71.42% antiepileptic activity). These results suggest that surface functionalized MSN are promising for sustained drug delivery for improved seizure control.