Item Details

title

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

author

Todd, Meagan E

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

Yazdani, Saami K (committee chair)

Soto-Pantoja, David R (committee member)

Saul, Justin (committee member)

date

2022-05-24T08:35:54Z (accessioned)

2023-05-23T08:30:11Z (available)

2022 (issued)

degree

Biomedical Science – MS (discipline)

embargo

2023-05-23 (terms)

identifier

http://hdl.handle.net/10339/100728 (uri)

language

en (iso)

publisher

Wake Forest University

type

Thesis