Study In Silico and Nanoparticle-Based Evaluation of Arbutinyl Undecylenate Targeting AChE and iNOS for Neuroprotection

Abstract

Alzheimer’s disease is a multifactorial neurodegenerative disorder involving cholinergic dysfunction, oxidative stress, and neuroinflammation. This study aimed to evaluate the neuroprotective potential of arbutinyl undecylenate through an integrated approach combining molecular modeling and nanoparticle formulation. Molecular docking and molecular dynamics simulations were performed to assess ligand interactions with acetylcholinesterase (AChE) and inducible nitric oxide synthase (iNOS). The results demonstrated that arbutinyl undecylenate exhibited favorable binding affinity toward both targets, with stable interaction profiles confirmed by RMSD, RMSF, radius of gyration, and hydrogen bonding analyses. MM-GBSA calculations further supported these findings, indicating favorable binding free energy, particularly toward iNOS. To enhance delivery, the compound was formulated into PLGA nanoparticles via emulsification. The nanoparticles exhibited a size range of approximately 176–191 nm, a polydispersity index of ~0.3, and a high entrapment efficiency (~97%). Morphological analysis confirmed the formation of spherical particles, while FTIR indicated no chemical interaction between the drug and the polymer. XRD and DSC analyses revealed a reduction in crystallinity, suggesting successful encapsulation in an amorphous or molecularly dispersed state. In conclusion, arbutinyl undecylenate demonstrates promising molecular interaction and can be effectively incorporated into PLGA nanoparticles with suitable physicochemical properties. This integrated strategy highlights the potential of combining molecular modification with nanotechnology-based delivery systems to develop neuroprotective agents. Further experimental validation is required to confirm its therapeutic applicability.