Rational development of a drug-delivery device based on MOF UiO-66 for calcium-channel-blocker drugs

Abstract

The administration of drugs with low solubility or absorption, such as the calcium-channel-blocker (CCB) drugs amlodipine, nifedipine, and nimodipine, affects the management of complicated health conditions related to cardiovascular diseases. The development of a drug-delivery device based on MOFs is a rising topic. Thus, in this work, the use of MOF UiO-66 as a platform to develop a drug-delivery device was analyzed using CCB drugs through an empirical and theoretical approach. Our results demonstrate that UiO-66 adsorb and release the three studied drugs without altering the chemical or physical properties of either the material or the drugs. Moreover, computational studies show that dispersive energies are key to the interaction of nimodipine and nifedipine with the material, providing a better understanding of the release behavior observed for each drug. Finally, the effect on the biological activity of the drugs was evaluated using human microvascular endothelial cells, demonstrating that the material can improve the bioavailability of each drug, allowing a 90% reduction in the doses needed to attain a physiological effect. These results support the potential of UiO-66 as a central component in the development of a versatile drug-delivery system aimed at improving the treatment of patients with cardiovascular diseases.