Design and characterization of memantine and donepezil loaded 3D scaffolds

Memantine HCl (MEM) and Donepezil HCl (DON) are widely used separately and in combination to treat Alzheimer's disease, and some studies suggest that these drugs may also prevent bone fractures and promote bone regeneration. For this purpose, we formulated fiber-based 3D scaffolds for local delivery of MEM/DON to improve the regeneration process of bone fractures. First, Poly (ε-caprolactone) (PCL)-based MEM/DON-loaded nanofibrous membranes were produced by electrospinning, and then these nanofibrous membranes were transformed into 3D scaffolds using the thermally induced self-agglomeration (TISA) method. Encapsulation efficiency after these two steps was found to be around 20%. Analyses confirmed that the 3D scaffolds have a morphology similar to the extracellular matrix, and that their hydrophilicity, swelling ratio, porosity, and degradation rate were adequate for bone tissue regeneration. Release studies show that the scaffolds provide an initial burst release of the drugs, followed by a sustained release for 21 days. These 3D scaffolds did not show any cytotoxic effect on the L-929 cell line, and increased cell viability over time indicates that they can be used in tissue engineering applications.