Development and in vitro evaluation of donepezil hydrochloride-loaded thermo-responsive polymer grafted molybdenum disulfide nanosheets: Modeling using response surface methodology

Nanocarriers are utilized to deliver bioactive substances in the treatment of neurodegenerative diseases such as Alzheimer's. In this work, we prepared donepezil hydrochloride-loaded molybdenum disulfide modified thermo-responsive polymer as the thermo-responsive nanocarrier. Then, glycine was grafted to the surface of the polymer to improve the targeting and sustained release. The morphology, crystallinity, chemical bonding, and thermal behavior of nanoadsorbent were fully characterized by field emission scanning electron microscopes, energy dispersive X-ray, X-ray diffraction, Fourier-transform infrared spectroscopy, and thermo-gravimetric measurement. Response surface methodology with the central composite design was applied to optimize the sorption key factors such as pH solution (A: 5-9), contact time (B: 10-30 min), and temperature (C: 30-50 °C). Non-linear isotherm modeling confirmed that the sorption of the drug follows the Ferundlich model based on higher correlation coefficient values (R² =0.9923) and lower errors values (root means square errors: 0.16 and Chi-square: 0.10), suggesting a heterogeneous multilayer surface sorption. The non-linear sorption kinetic modeling revealed that the pseudo-second-order kinetic model well-fitted the sorption data of the drug on the nanoadsorbent surface based on higher R² values (R² =0.9876) and lower errors values (root means square errors: 0.05 and Chi-square: 0.02). The in vitro drug release experiment of donepezil hydrochloride shown that about 99.74 % of drug release was found to be occurred at pH= 7.4 (T = 45 °C) within 6 h, whereas about 66.32 % of drug release occurred at pH= 7.4 (T = 37 °C). The release of donepezil hydrochloride from as prepared drug delivery system has shown a sustained release profile, which was fitted to Korsmeyer-Peppas kinetics.