An Implantable Artificial Atherosclerotic Plaque as a Novel Approach for Drug Transport Studies on Drug‐Eluting Stents. Issue 6 (16th December 2021)

• Record Type: Journal Article
• Authors: Razzi, Francesca; Lovrak, Matija; Gruzdyte, Dovile; Den Hartog, Yvette; Duncker, Dirk J.; van Esch, Jan H.; van Steijn, Volkert; van Beusekom, Heleen M. M.
• Is Part Of: Advanced healthcare materials. Volume 11:Issue 6(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-12-16
• Subjects: arterial drug transport -- atherosclerosis -- drug‐eluting stents -- hydrogels -- MALDI imaging; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1002/adhm.202101570
• Languages: English
• ISSNs: 2192-2640

Abstract

Abstract: Atherosclerotic arteries are commonly treated using drug‐eluting stents (DES). However, it remains unclear whether and how the properties of atherosclerotic plaque affect drug transport in the arterial wall. A limitation of the currently used atherosclerotic animal models to study arterial drug distribution is the unpredictability of plaque size, composition, and location. In the present study, the aim is to create an artificial atherosclerotic plaque—of reproducible and controllable complexity and implantable at specific locations—to enable systematic studies on transport phenomena of drugs in stented atherosclerosis‐mimicking arteries. For this purpose, mixtures of relevant lipids at concentrations mimicking atherosclerotic plaque are incorporated in gelatin/alginate hydrogels. Lipid‐free (control) and lipid‐rich hydrogels (artificial plaque) are created, mounted on DES and successfully implanted in porcine coronary arteries ex‐vivo. Matrix‐assisted laser desorption ionization mass spectrometry imaging (MALDI‐MSI) is used to measure local drug distribution in the arterial wall behind the prepared hydrogels, showing that the lipid‐rich hydrogel significantly hampers drug transport as compared to the lipid‐free hydrogel. This observation confirms the importance of studying drug transport phenomena in the presence of lipids and of having an experimental model in which lipids and other plaque constituents can be precisely controlled and systematically studied. Abstract : The aim of this work is to create an implantable artificial atherosclerotic plaque of reproducible and controllable composition. Mixtures of relevant lipids are incorporated in gelatin/alginate hydrogels, which are mounted on DES and implanted in swine coronary arteries ex‐vivo. Drug concentrations in the arterial wall behind the plaque show that the lipid‐rich hydrogel hampers drug transport as compared to the lipid‐free hydrogel.