Pre-Clinical Investigation of Liquid Paclitaxel for Local Drug Delivery: A Pilot Study.

Claire V Cawthon,Estefanny Villar-Matamoros,Lauren Stokes,Saami K Yazdani,Alyssa Lloret,Uwe Christians,Clifton Huett,Michele Schuler,Kathryn Cooper

doi:10.3390/ph13120434

Abstract

The purpose of this pilot study was to investigate the feasibility of a perfusion catheter to deliver liquid paclitaxel into arterial segments. A clinically relevant rabbit ilio-femoral injury model was utilized to determine the impact of liquid paclitaxel delivered locally into the vessel wall using a perfusion catheter at 1 h to 14 days. Treatment by two clinically available forms of liquid paclitaxel, a solvent-based (sb) versus an albumin-bound (nab), along with a control (uncoated balloons), were investigated. Pharmacokinetic results demonstrated an increase in the retention of the sb-paclitaxel versus the nab-paclitaxel at 1 h; however, no other differences were observed at days one, three, and seven. Histological findings at 14 days showed significantly less neointimal area in the sb-paclitaxel treated arteries as compared with the nab-paclitaxel and the uncoated balloon-treated arteries. Additionally, percent area stenosis was significantly less in the sb-paclitaxel group. These results support the concept of local liquid delivery of paclitaxel into the arterial segments.

Highlights

There are more than three million people affected by peripheral artery disease (PAD) every year in the U.S Disparate from coronary artery disease, PAD is characterized by a substantial plaque burden and often presents with long and complex lesions [1,2]
The nab-paclitaxel and sb-paclitaxel were successfully delivered to the external iliac arteries using the perfusion catheter
Our overall results support the concept of local liquid delivery of paclitaxel into the arterial segments

Summary

Introduction

There are more than three million people affected by peripheral artery disease (PAD) every year in the U.S Disparate from coronary artery disease, PAD is characterized by a substantial plaque burden and often presents with long and complex lesions [1,2]. Endovascular treatment of PAD focuses first on re-establishing blood flow by angioplasty and, more frequently, de-bulking by atherectomy. Angioplasty, described as a control injury, expands the lumen by outward stretching of the arterial wall. The vascular smooth muscle cells (VSMCs), residing in the vessel wall, respond to this injury by proliferating and migrating inward, re-narrowing the vessel lumen. To minimize the injury response and to inhibit VSMC proliferation, anti-proliferative drugs have been locally delivered using drug-eluting stents (DES) or drug-coated balloons (DCBs) [3,4]

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Results

Discussion

Conclusion