Transdermal Delivery of Donepezil Niosomes For Alzheimer's Disease: Synthesis, Ex Vivo Permeation And Brain Targeting Studies.

Abstract

The present investigation aims to encapsulate donepezil (DNP) in niosomes to avert the side effects and deliver the drug to the brain bypassing the skin barrier. The finding conclusively demonstrated that entrapment efficiency and the alteration in the niosome size are associated with the change in the span 60: cholesterol ratio, sonication, hydration volume, and Solulan C24. The optimization process resulted in the formation of stable niosomes of 180.1 ± 1.83 nm entrapping 82.15% ± 1.54% of the drug. The cryo-SEM image and in vitro drug release profile revealed that the optimized niosome is pH-sensitive, and the niosomes undergo membrane destabilization at acidic skin pH. The MN-assisted studies with MN1200 showed a 26-fold increase in transdermal permeation of DNP against the passive method in porcine skin at a steady flux rate of 9.89 ± 0.923 μg/cm2/h. Therefore, it may be inferred that delivering the intact DNP niosomes using MNs across the skin is feasible by a relatively painless and non- invasive method, thereby improving patient compliance. The specificity of a niosome for brain cells was improved by functionalizing the niosomes with NPG, a glucose analog molecule. The molecular docking computational studies identified the interacting amino acids between the NPG ligand and active site, 4PYP of the GLUT-1 transporter protein. In addition, the cell viability studies by AO-EB staining and cell uptake studies by the iron perls staining method presented visual evidence for non-toxicity and internalization of the niosomes. The in vivo studies on AD-induced SD rats demonstrated excellent localization and sustained release of DNP from NPG-fn-niosome by three folds. The results confirmed the actual effectiveness of NPG functionalization and site-directed delivery. However, further preclinical studies are recommended to confirm the efficacy of the engineered drug delivery system.