In-silico study of drug delivery to atherosclerosis in the human carotid artery using metal–organic frameworks based on adhesion of nanocarriers

Abstract

Abstract This study investigates nanocarriers (NCs) for drug delivery targeting carotid artery atherosclerosis. This targeted drug delivery mechanism is based on ligand–receptor bindings facilitated by coating NCs with P-selectin aptamers, which exhibit high affinities for P-selectin plaque receptors. Recognizing the significant advantages of metal–organic frameworks (MOFs), such as their high drug-loading percentages, we chose them as nanocarriers for this research. Our evaluation considers critical factors: NC surface density (the number of attached nanocarriers per unit of plaque area), toxicity (percentage of NCs missing the target), and efficient drug transfer to plaque tissue. Employing molecular dynamics (MD) for drug loading calculations via van der Waals interactions and computational fluid dynamics (CFD) for toxicity, surface density, and drug transfer assessments, we achieve a comprehensive analysis. A cardiac cycle-based metric guides optimal MOF release conditions, establishing an ideal dosage of 600 NCs per cycle. MOF-801 exhibits outstanding drug delivery performance, particularly in plaque targeting. While a magnetic field enhances NC adhesion, its impact on drug transfer is limited, emphasizing the need for further optimization in magnetic targeting for NC-based therapies. This study provides crucial insights into NC drug delivery performance in carotid artery atherosclerosis, advancing the field of targeted drug delivery for atherosclerosis treatment.