Development and in Vitro Characterization of Photochemically Crosslinked Polyvinylpyrrolidone Coatings for Drug-Coated Balloons

Svea Petersen,Katrin Sternberg,Ingo Minrath,Sebastian Kaule,Jürgen Köcher,Klaus-Peter Schmitz

doi:10.3390/coatings3040253

Abstract

Polyvinylpyrrolidone (PVP) is a conventionally applied hydrophilic lubricious coating on catheter-based cardiovascular devices, used in order to ease movement through the vasculature. Its use as drug reservoir and transfer agent on drug-coated balloons (DCB) is therefore extremely promising with regard to the simplification of its approval as a medical device. Here, we developed a PVP-based coating for DCB, containing paclitaxel (PTX) as a model drug, and studied the impact of crosslinking via UV radiation on drug stability, wash off, and transfer during simulated use in an in vitro vessel model. We showed that crosslinking was essential for coating stability and needed to be performed prior to PTX incorporation due to decreased drug bioavailability as a result of photodecomposition and/or involvement in vinylic polymerization with PVP under UV radiation. Moreover, the crosslinking time needed to be carefully controlled. While short radiation times did not provide enough coating stability, associated with high wash off rates during DCB insertion, long radiation times lowered drug transfer efficiency upon balloon expansion. A ten minutes radiation of PVP, however, combined a minimized drug wash off rate of 34% with an efficient drug transfer of 49%, underlining the high potential of photochemically crosslinked PVP as a coating matrix for DCB.

Highlights

The use of percutaneous, catheter-based vascular devices to treat coronary and peripheral artery disease, caused by arteriosclerosis, has become the standard of care
We developed and thoroughly characterized a PTX containing PVP coating for drug-coated balloons (DCB) with regard to in vitro drug wash off and transfer upon expansion
Crosslinking of PVP evidenced essential for reduction of PTX wash off rates during insertion of the DCB to the vasculature and, thereby, for efficient drug transfer

Summary

Introduction

The use of percutaneous, catheter-based vascular devices to treat coronary and peripheral artery disease, caused by arteriosclerosis, has become the standard of care. As PTX alone is very lipophilic and, sticks to the balloon surface, transfer agents, as the mainly studied contrast agent iopromide [6], and urea [7] and plasticizers [8], are applied in order to enhance the drug transfer capability. These are generally mixed in a varying content with the drug in an applicable solvent, and the resulting solutions/suspensions are deposited to the balloon surface by means of one of the numerous established coating approaches for vascular implants, mainly micropipetting, dip-coating, and spray-coating [9]. While Kelsch et al [11] reported percental PTX wash off rates of up to 26% and 36% for urea- or iopromide-based DCB, respectively, Berg et al [12]

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