Carboxymethylcellulose encapsulated fingolimod, siRNA@ZnO hybrid nanocomposite as a new anti-Alzheimer's material

Abstract

Alzheimer's disease (AD) is a fatal neurological disorder that causes cognitive and memory function to deteriorate. A critical pathogenic event that speeds up the development of AD is the interaction between dysfunctional microglia and amyloid-β (Aβ). We have developed a hybrid nanocomposite material to treat AD by normalizing the dysfunctional microglia. The material is based on carboxymethylcellulose (CMC) encapsulated fingolimod, siRNA, and zinc oxide (ZnO) with variable loading (CMC-Fi-siRNA@ZnO_a–d). The material was characterized using different techniques including FTIR, XRD, thermal analysis, SEM with EDX, and TEM micrographs. The chemical structure was confirmed by FTIR and XRD analyses, which indicated the successful integration of ZnO nanoparticles (NPs) into the polymer matrix, signifying a well-formed composite structure. The thermal stability order at 10% weight loss was CMC-Fi-siRNA@ZnO_c > CMC-Fi-siRNA@ZnO_b > CMC-Fi-siRNA@ZnO_d > CMC-Fi-siRNA@ZnO_a. The CMC-Fi-siRNA@ZnO_d dramatically alleviates the priming of microglia by lowering the level of proinflammatory mediators and increasing the secretion of BDNF. This considerably improves the phagocytosis of Aβ. In the cell viability test in immortalized microglia cells (IMG), the hybrid nanocomposite (NP) exhibited no significant effect on cell survival after 48 hours of incubation. The NP also decreased the cytotoxicity caused by Aβ. Therefore, the CMC-hybrid NP has high potential as a drug delivery system in the development of therapeutic strategies for AD.