In vitro and in vivo evaluation of effect of excipients in local delivery of paclitaxel using microporous infusion balloon catheters

详细信息    查看全文

• 作者：Jordan A. Anderson ; Tyler Remund ; Kathryn Pohlson ; Sujan Lamichhane ; Claire Evans ; Rick Evans ; Melanee Clark ; Kristi Egland ; Patrick Kelly and Gopinath Mani
• 刊名：Journal of Biomedical Materials Research Part B: Applied Biomaterials
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：105
• 期：2
• 页码：376-390
• 全文大小：1319K
• ISSN：1552-4981

文摘

Drug-infusion balloons are one of the currently used local drug delivery devices for preventing restenosis after endovascular treatments. An antiproliferative drug (paclitaxel, PAT) is infused through the balloon using a cremophor-based formulation to control restenosis. However, the major limitations of this approach are poor in vivo drug uptake and a limit in the amount of PAT delivered because of cremophor toxicity. In this study, we have investigated the use of different excipients for effectively infusing PAT out of the balloon for improved drug uptake in the tissue. The excipients include nanoparticle albumin-bound PAT (nab-PAT, a nanobiomaterial used in cancer therapy), urea (a hydrophilic agent used for faster drug transfer), iodixanol (a contrast agent used for coronary angiography), and cremophor-PAT (the most commonly used PAT formulation). An in vitro drug release, smooth muscle cell (SMC) response, endothelial cell (EC) response, and in vivo drug uptake were investigated for all the different excipients of PAT infused through the balloon. The nab-PAT was as effective as cremophor in infusing out of the balloon and inhibiting SMC growth. Also, nab-PAT showed a significantly greater amount of in vivo PAT uptake than that of cremophor-PAT. Urea and iodixanol were not effective in delivering a clinically relevant dose of PAT due to the poor solubility of PAT in these excipients. Urea eradicated all the SMCs and ECs, suggesting a toxic effect, which impedes its use in balloon-based therapy. Thus, this study demonstrated that nab-PAT is an effective formulation to locally deliver PAT through infusion balloons.