Protective activity of bacopaside I encapsulated polymeric nanoparticles against kainic acid-induced excitotoxicity

Bacopaside I (BM4), a saponin found in <i>Bacopa monnieri</i>, has nootropic, neuroprotective, and anti-depressant properties. Neuroprotective entities generally are impermeable across the brain membrane, and this hassle can be resolved by using drug-encapsulated polymeric nanoparticles (NPs). Epileptic seizures are linked to the increased expression of fractalkine, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors, and mammalian target of rapamycin (mTOR) dysregulation. This study investigated the effect of BM4 encapsulated poly(lactic-co-glycolic acid) (PLGA)-polyethylene glycol (PEG)-nanoparticles (BM4NP) in comprehending seizure and its ability to protect brain tissues from kainic acid (KA)-induced excitotoxicity associated neuroinflammation, oxidative stress, and over-expression of seizure markers. The optimal size (87.31 ± 9.2 nm) and zeta potential (-18.8 ± 4.7 mV) of BM4NP resulted in efficient drug loading and release kinetics. Our data demonstrated that BM4NP reduced KA-induced brain tissue damage, by restoring normal nuclear outline and strengthening brain membrane integrity. BM4NP also suppressed the over-expression of fractalkine, AMPA receptors, and mTORC1 signaling and increased antioxidant levels, suggesting it as a therapeutic agent to contain seizures.