Memantine loaded micro/nanoscale magnetic motors for the treatment of Alzheimer's Disease

Abstract

Micro/nanomotors (MNM) are self-propelled devices operating at the nano or microscale, offering significant potential for applications such as drug delivery, cell manipulation, bio-imaging, diagnostics, and environmental remediation. In this study, we report for the first time the development of novel, magnetically actuated MNMs loaded with Memantine (Mem) toward the treatment of Alzheimer's Disease (AD). AD, a neurodegenerative disease with no cure, presents a significant challenge due to its increasing prevalence. This research aimed to design a targeted drug delivery system using Mem, a common AD treatment, loaded onto magnetically maneuverable MNMs. The fabricated Mem-loaded MNMs were thoroughly characterized in terms of morphology, particle size, drug loading efficiency, magnetic actuation and in vitro drug release kinetics. The final formulation exhibited a drug loading efficiency of 14.06 ± 5.2 % and achieved 95 ± 2.4 % drug release within 72 h. The average velocity of the Mem loaded magnetically propelled MNMs was determined as 16.3 ± 2.3 μm/s. Cytotoxicity assessments in SH-SY5Y cells confirmed the non-toxicity of the MNM formulation (77.08 ± 2.5 % viability at 48 h), while efficacy studies demonstrated significant BACE1 inhibition and TrkB upregulation, with superior blood brain barrier (BBB) model suppression versus Mem solution, indicating potential for enhanced BBB drug delivery and therapeutic benefit. Metabolomic analysis corroborated these findings, showing alterations in glutathione, asparagine, phosphatidylcholine, and phosphatidylinositol levels, consistent with AD-related metabolic changes. In vivo biodistribution in Balb-C mice showed significant MNM brain accumulation within 30 min. Altogether, this study suggests that magnetically actuated, Mem-loaded MNMs represent a promising strategy for leveraging efforts in managing Alzheimer's Disease through enhanced, site-specific drug delivery approaches.