Anti-excitotoxicity and neuroprotective action of asiaticoside encapsulated polymeric nanoparticles in pilocarpine rodent seizure model

Abstract

Asiaticoside (ASI), an ursane-type triterpenoid saponin, isolated from the memory enhancing herb Centella asiatica, is known for its neuroprotective activities. Here, the anti-excitotoxicity and neuroprotective effects of ASI encapsulated alginate chitosan nanoparticles (ACNPs) were evaluated in pilocarpine (PC) induced seizure in mice model. ACNPs were prepared by ionic gelation-polyelectrolyte complex method and their physicochemical characterization was carried out by TEM, SEM, DLS, XRD, and FTIR. Subsequently, their encapsulation efficiency (EE), in vitro drug release, cell viability, seizure score, DNA fragmentation, and mRNA expression of regulatory stress markers were evaluated. Membrane permeability of ACNPs in the brain, histopathology, and biological TEM and SEM analyses were also carried out. TEM of ACNPs showed spherical morphology with a particle size of 200–400 nm. DLS of ACNPs displayed an average size of 486.2 nm with polydispersity index (PDI) of 0.567 and zeta potential of –14.1 mV. ACNPs achieved high EE (>90%) and controlled release (10%). Biological evaluation studies revealed ACNPs as non-toxic to mouse neural stem cells (mNSCs). They displayed enhanced brain permeability and attenuated seizure. Our results confirmed ACNPs as effective in crossing the brain membrane barrier and mitigating seizure severity induced by PC.