1. Pre-Clinical Investigation of Keratose as an Excipient of Drug Coated Balloons
- Author
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Claire V. Cawthon, Randolph L. Geary, Megan Erwin, Onree Wilson, Justin M. Saul, Emily Goel, Uwe Christians, Saami K. Yazdani, Thomas C. Register, Nathaniel Fedor, Trevor Rayl, and Carson Schaff
- Subjects
Pulsatile flow ,Drug Evaluation, Preclinical ,Pharmaceutical Science ,02 engineering and technology ,030204 cardiovascular system & hematology ,Balloon ,Analytical Chemistry ,chemistry.chemical_compound ,0302 clinical medicine ,Drug Delivery Systems ,Coating ,Coated Materials, Biocompatible ,Drug Discovery ,Drug Carriers ,Keratose ,021001 nanoscience & nanotechnology ,Immunohistochemistry ,Paclitaxel ,Chemistry (miscellaneous) ,Drug delivery ,Molecular Medicine ,endovascular ,0210 nano-technology ,medicine.drug ,Drug coated balloon ,pre-clinical ,drug-coated balloon ,Excipient ,Antineoplastic Agents ,engineering.material ,Article ,lcsh:QD241-441 ,03 medical and health sciences ,Peripheral Arterial Disease ,lcsh:Organic chemistry ,medicine ,Animals ,Physical and Theoretical Chemistry ,business.industry ,Organic Chemistry ,Cardiovascular Agents ,Keratosis ,chemistry ,drug delivery ,engineering ,business ,Ex vivo ,Angioplasty, Balloon ,Biomedical engineering - Abstract
Background: Drug-coated balloons (DCBs), which deliver anti-proliferative drugs with the aid of excipients, have emerged as a new endovascular therapy for the treatment of peripheral arterial disease. In this study, we evaluated the use of keratose (KOS) as a novel DCB-coating excipient to deliver and retain paclitaxel. Methods: A custom coating method was developed to deposit KOS and paclitaxel on uncoated angioplasty balloons. The retention of the KOS-paclitaxel coating, in comparison to a commercially available DCB, was evaluated using a novel vascular-motion simulating ex vivo flow model at 1 h and 3 days. Additionally, the locoregional biological response of the KOS-paclitaxel coating was evaluated in a rabbit ilio-femoral injury model at 14 days. Results: The KOS coating exhibited greater retention of the paclitaxel at 3 days under pulsatile conditions with vascular motion as compared to the commercially available DCB (14.89 ±, 4.12 ng/mg vs. 0.60 ±, 0.26 ng/mg, p = 0.018). Histological analysis of the KOS&ndash, paclitaxel-treated arteries demonstrated a significant reduction in neointimal thickness as compared to the uncoated balloons, KOS-only balloon and paclitaxel-only balloon. Conclusions: The ability to enhance drug delivery and retention in targeted arterial segments can ultimately improve clinical peripheral endovascular outcomes.
- Published
- 2020