PHARMACOLOGICAL EVALUATION OF METHYSTICIN-LOADED NANOPARTICLES IN AlCl3 INDUCED ALZHEIMER'S DISEASE

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by extracellular amyloid-beta accumulation, neurofibrillary tangles, and severe neuroinflammation. Methysticin, a bioactive kavalactone derived from Piper methysticum, possesses potent neuroprotective and anti-inflammatory properties; however, its clinical translation is limited by poor aqueous solubility, rapid hepatic metabolism, and restricted blood–brain barrier (BBB) penetration. Here, we developed methysticin-loaded poly(lactic-co-glycolic acid) nanoparticles (MN–PLGA NPs) to overcome these biopharmaceutical constraints. In silico modeling confirmed high passive BBB permeability ( ; ) and strong binding affinities of methysticin toward  ( ) and  ( ). Dynamic light scattering demonstrated successful nanoparticle synthesis with an optimal hydrodynamic diameter ( ), narrow polydispersity index ( ), stable negative surface charge ( ), high encapsulation efficiency ( ), and effective drug loading ( ). -induced neurodegenerative mice model (  for 42 days), was followed . Quantitative RT-PCR analysis demonstrated that MN–PLGA NPs achieved significantly greater down-regulation of elevated  mRNA expression compared to unformulated methysticin. These results establish that PLGA-mediated nanoencapsulation enhances the anti-inflammatory potency of methysticin by promoting sustained delivery and improved CNS permeation, offering a promising nanotherapeutic platform for AD management in support of Sustainable Development Goal 3.