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The Delivery and Retention of Sirolimus in ex vivo Porcine Carotid Artery for Treatment of Restenosis

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abstract
In recent years, controversial findings regarding the long-term safety profile of paclitaxel-coated balloons and paclitaxel-eluting stents have raised concerns among the cardiovascular community and pushed researchers to investigate alternative therapeutics and modes of delivery for the treatment of peripheral artery disease (PAD). Liquid drug delivery (LDD) devices once dominated the market as delivery systems for anticoagulants like heparin, but as advancements were made in stent and balloon delivery platforms, the preferred choice of therapeutic also shifted toward antiproliferatives like paclitaxel and sirolimus. Paclitaxel has long since been the leading antiproliferative used for treatment of PAD, delivered primarily via drug-coated balloons. Meanwhile, the use of sirolimus has been limited to coronary interventions and cancer therapeutics, as its poor bioavailability and reversible binding mechanisms make it more difficult to deliver and retain within the arterial wall. The four LDD systems examined in this study have exhibited favorable safety and efficacy profiles following successful delivery of liquid therapeutics to target lesions in both preclinical and clinical trials. Within the ex-vivo bioreactor system utilized in this study, it has been shown that sirolimus is capable of being delivered via LDD and retained within the tissue of an explanted porcine carotid artery. The addition of the excipients probucol and butylated hydroxytoluene to the liquid solutions containing sirolimus served to increase the average tissue sirolimus concentration at the 1-hour time-point, thereby increasing the uptake of sirolimus in the ex-vivo model.
subject
Cardiovascular
Liquid
Paclitaxel
Peripheral
Restenosis
Sirolimus
contributor
Todd, Meagan E (author)
Yazdani, Saami K (committee chair)
Soto-Pantoja, David R (committee member)
Saul, Justin (committee member)
date
2022-05-24T08:35:54Z (accessioned)
2022 (issued)
degree
Biomedical Science – MS (discipline)
2023-05-23 (liftdate)
embargo
2023-05-23 (terms)
identifier
http://hdl.handle.net/10339/100728 (uri)
language
en (iso)
publisher
Wake Forest University
title
The Delivery and Retention of Sirolimus in ex vivo Porcine Carotid Artery for Treatment of Restenosis
type
Thesis

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