Purpose: Drug coated balloons (DCB) are continually improving due to advances in\ncoating techniques and more effective excipients. Paclitaxel, the current drug choice of\nDCB, is a microtubule-stabilizing chemotherapeutic agent that inhibits smooth muscle\ncell proliferation. Excipients work to promote coating stability and facilitate paclitaxel\ntransfer and retention at the target lesion, although current excipients lack sustained,\nlong-term paclitaxel retention. Keratose, a naturally derived protein, has exhibited unique\nproperties allowing for tuned release of various therapeutic agents. However, little\nis known regarding its ability to support delivery of anti-proliferative agents such as\npaclitaxel. The goal of this project was to thus demonstrate the feasibility of keratose\nas a DCB-coating excipient to promote the release and delivery of paclitaxel.\nMethods: Keratose was combined with paclitaxel in vitro and the release kinetics of\npaclitaxel and keratose were evaluated through high performance liquid chromatographmass\nspectroscopy (HPLC-MS) and spectrophotometry, respectively. A custom coating\nmethod was developed to deposit keratose and paclitaxel on commercially available\nangioplasty balloons via an air spraying method. Coatings were then visualized under\nscanning electron microscopy and drug load quantified by HPLC-MS. Acute arterial\ntransfer of paclitaxel at 1 h was assessed using a novel ex vivo model and further\nevaluated in vivo in a porcine ilio-femoral injury model. ... Results: Keratose demonstrated tunable release of paclitaxel as a function of keratose\nconcentration in vitro. DCB coated via air spraying yielded consistent drug loading Under scanning electron microscopy, the keratose-paclitaxel\nDCB showed uniform coverage with a consistent, textured appearance. The acute drug\ntransfer of the keratose-paclitaxel DCB was 43.60 ... 14.8 ng/mg at 1 h ex vivo. These\nmeasurements were further confirmed in vivo as the acute 1 h arterial paclitaxel levels\nwere .... Conclusion: The keratose-paclitaxel coated DCB exhibited paclitaxel uptake and\nachieved acute therapeutic arterial tissue levels, confirming the feasibility of keratose\nas a novel excipient for DCB.
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