Production, characterization, and in vitro evaluation of anti-Alzheimer's Memantine/Donepezil/Metformin-loaded PVA/PEO composite nanofibers by pressurized gyration

Abstract

In this study, memantine (MM) and donepezil (DO) were combined with metformin (MF) as a new approach for the Alzheimer’s disease (AD) treatment sublingually. MM/DO/MF loaded to polyvinyl alcohol (PVA)/polyethylene oxide (PEO) composite nanofibers (NFs) in three different ratios (9/1, 8/2, and 7/3) by pressurized gyration. The diameter of fibers was decreased by reducing the PEO ratios and adding the drugs in polymer solutions. MM, DO, and MF were successfully loaded and distributed in NFs by the results of FTIR, XRD, and DSC tests. The drug release percentages enhanced with an increasing ratio of PVA in fibers by the dissolution test results. All fibers at various ratios were found suitable for the sublingual route by disintegrating quickly. No significant toxicity of nanofibers at 24 and 48 h was observed on SH-SY5Y cells. The highest neuroprotection activity was observed in the cells treated with MM/DO/MF-loaded NFs at 7/3. The mRNAs of APP and BACE-1 of the MM/DO/MF-loaded NF group were lower than those of the Aβ1-42 group while, ADAM-10 mRNA expression increased in the MM/DO/MF-loaded NFs treatment group via PCR results. The morphological structure of the cells treated with the MM/DO/MF-loaded NFs was protected from Aβ1-42-induced neurotoxicity by confocal laser scanning microscopy images.