title: In vitro and in vivo evaluation of effect of excipients in local delivery of paclitaxel using microporous infusion balloon catheters.
abstract: 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. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 376-390, 2017.
authors.affiliation: Biomedical Engineering, The University of South Dakota, Sioux Falls, South Dakota, 57107.
authors.forename: Jordan A
authors.initials: JA
authors.lastname: Anderson
authors.affiliation: Sanford Research, Sioux Falls, South Dakota, 57104.
authors.forename: Tyler
authors.initials: T
authors.lastname: Remund
authors.affiliation: Sanford Research, Sioux Falls, South Dakota, 57104.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Pohlson
authors.affiliation: Biomedical Engineering, The University of South Dakota, Sioux Falls, South Dakota, 57107.
authors.forename: Sujan
authors.initials: S
authors.lastname: Lamichhane
authors.affiliation: Sanford Research, Sioux Falls, South Dakota, 57104.
authors.forename: Claire
authors.initials: C
authors.lastname: Evans
authors.affiliation: Sanford Research, Sioux Falls, South Dakota, 57104.
authors.forename: Rick
authors.initials: R
authors.lastname: Evans
authors.affiliation: Sanford Research, Sioux Falls, South Dakota, 57104.
authors.forename: Melanee
authors.initials: M
authors.lastname: Clark
authors.affiliation: Sanford Research, Sioux Falls, South Dakota, 57104.
authors.forename: Kristi
authors.initials: K
authors.lastname: Egland
authors.affiliation: Sanford Health, Sioux Falls, South Dakota, 57105.
authors.forename: Patrick
authors.initials: P
authors.lastname: Kelly
authors.affiliation: Biomedical Engineering, The University of South Dakota, Sioux Falls, South Dakota, 57107.
authors.forename: Gopinath
authors.initials: G
authors.lastname: Mani
mesh_terms: D057785:Catheters; D016503:Drug Delivery Systems / Q000379:methods*; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*; D017239:Paclitaxel / Q000494:pharmacology*; D016062:Porosity
chemical_list: D017239:Paclitaxel
keywords: Drug infusion balloons; paclitaxel; peripheral artery disease; restenosis; smooth muscle cells