000118814 001__ 118814
000118814 005__ 20240319081006.0
000118814 0247_ $$2doi$$a10.1016/j.jconrel.2022.07.037
000118814 0248_ $$2sideral$$a130009
000118814 037__ $$aART-2022-130009
000118814 041__ $$aeng
000118814 100__ $$aMcQueen, A.
000118814 245__ $$aAn intricate interplay between stent drug dose and release rate dictates arterial restenosis
000118814 260__ $$c2022
000118814 5060_ $$aAccess copy available to the general public$$fUnrestricted
000118814 5203_ $$aSince the introduction of percutaneous coronary intervention (PCI) for the treatment of obstructive coronary artery disease (CAD), patient outcomes have progressively improved. Drug eluting stents (DES) that employ anti-proliferative drugs to limit excess tissue growth following stent deployment have proved revolutionary. However, restenosis and a need for repeat revascularisation still occurs after DES use. Over the last few years, computational models have emerged that detail restenosis following the deployment of a bare metal stent (BMS), focusing primarily on contributions from mechanics and fluid dynamics. However, none of the existing models adequately account for spatiotemporal delivery of drug and the influence of this on the cellular processes that drive restenosis. In an attempt to fill this void, a novel continuum restenosis model coupled with spatiotemporal drug delivery is presented. Our results indicate that the severity and time-course of restenosis is critically dependent on the drug delivery strategy. Specifically, we uncover an intricate interplay between initial drug loading, drug release rate and restenosis, indicating that it is not sufficient to simply ramp-up the drug dose or prolong the time course of drug release to improve stent efficacy. Our model also shows that the level of stent over-expansion and stent design features, such as inter-strut spacing and strut thickness, influence restenosis development, in agreement with trends observed in experimental and clinical studies. Moreover, other critical aspects of the model which dictate restenosis, including the drug binding site density are investigated, where comparisons are made between approaches which assume this to be either constant or proportional to the number of smooth muscle cells (SMCs). Taken together, our results highlight the necessity of incorporating these aspects of drug delivery in the pursuit of optimal DES design. © 2022 The Authors
000118814 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000118814 590__ $$a10.8$$b2022
000118814 592__ $$a1.844$$b2022
000118814 591__ $$aCHEMISTRY, MULTIDISCIPLINARY$$b21 / 178 = 0.118$$c2022$$dQ1$$eT1
000118814 593__ $$aPharmaceutical Science$$c2022$$dQ1
000118814 591__ $$aPHARMACOLOGY & PHARMACY$$b11 / 278 = 0.04$$c2022$$dQ1$$eT1
000118814 594__ $$a17.1$$b2022
000118814 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000118814 700__ $$0(orcid)0000-0001-7620-3355$$aEscuer, J.
000118814 700__ $$aSchmidt, A. F.
000118814 700__ $$aAggarwal, A.
000118814 700__ $$aKennedy, S.
000118814 700__ $$aMcCormick, C.
000118814 700__ $$aOldroyd, K.
000118814 700__ $$aMcGinty, S.
000118814 773__ $$g349 (2022), 992-1008$$pJ. control. release$$tJOURNAL OF CONTROLLED RELEASE$$x0168-3659
000118814 8564_ $$s3844343$$uhttps://zaguan.unizar.es/record/118814/files/texto_completo.pdf$$yVersión publicada
000118814 8564_ $$s2478132$$uhttps://zaguan.unizar.es/record/118814/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000118814 909CO $$ooai:zaguan.unizar.es:118814$$particulos$$pdriver
000118814 951__ $$a2024-03-18-14:39:47
000118814 980__ $$aARTICLE