A novel high-efficiency transdermal patches for combinational therapy of Alzheimer's disease: Donepezil/vitamin B12-loaded nanofibers

Improving clinical practice in disease-modifying therapies is an important strategy in coping with the progressive course of Alzheimer's Disease (AD). This study aimed to develop DO and VB12-loaded nanofibers (DO/VB12-loaded NFs) as a transdermal drug delivery system, examine physicochemical properties, and evaluate the in vitro anti-Alzheimer's activity. DO/VB12-loaded NFs were produced with enhanced properties and a smooth structure without bead formation by the pressured gyration method. The drugs showed rapid release from DO/VB12-loaded NFs on the first day followed by sustained release for 14 days, indicating their suitability for transdermal application. Furthermore, the anti-Alzheimer's potential of DO/VB12-loaded NFs was investigated in a wide range using the functional ability of mitochondria (MTT) and viability analysis in amyloid-β (Aβ)-induced SH-SY5Y cells. The in vitro AD activity of DO/VB12-loaded NFs has been demonstrated as they are not cellular cytotoxic, promote viability in SH-SY5Y cells against Aβ1-42-induced neurotoxicity, and decrease gene expressions of APP and BACE-1, increase ADAM-10. In addition, cell morphology was visualized by confocal microscopy after treatment with DO/VB12-loaded NFs. Overall, those data showed that the designed NFs are a promising alternative to deliver DO and VB12 transdermally for the treatment of AD.