Design and characterization of memantine and donepezil loaded 3D scaffolds

abstract

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 (epsilon-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.

keywords

IN-VITRO; DRUG-DELIVERY; OSTEOGENIC DIFFERENTIATION; ELECTROSPUN NANOFIBERS; CONTROLLED-RELEASE; PORE-SIZE; SUSTAINED-RELEASE; POLYCAPROLACTONE; FIBERS; BLEND

subject category

Pharmacology & Pharmacy

authors

Ince, BT; Guieu, S; Timur, SS; Reçber, T; Nemutlu, E; Fernandes, MHV; Eroglu, H

our authors

acknowledgements

The authors thank The Scientific and Technology Research Council of Turkey for their support with the 2214/A Fellowship Program, the University of Aveiro, and the FCT for the support to the LAQV-REQUIMTE (UID/50006 -Laboratorio Associado para a Quimica Verde - Tecnologias e Processos Limpos), to the CICECO-Aveiro Institute of Materials (UID/CTM/50011/2019, UIDB/50011/2020 & UIDP/50011/2020), and to SG contract (2022.00751.CEECIND/CP1720/CT0046).

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