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.
|Journal||Advanced healthcare materials|
|Publication status||Published - 16 Mar 2022|
H.M.M.v.B. and V.v.S. contributed equally to this work. This study was supported by Grants ZonMw (91113020) to H.M.M.v.B., ZonMW (114021510) to H.M.M.v.B. and V.v.S., VENI NWO-STW (13137) to V.v.S., FP7 Marie Curie ETN “Smartnet” (316656) to M.L. and J.v.E. G. Springeling is thanked for his help in designing the perfusion chamber and preparing the artist's illustrations. P.C. Burgers is thanked for his indispensable help with MALDI-MS imaging.
© 2021 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH