Drug-coated balloons (DCB), which have emerged as a therapeutic alternative to drug-eluting stents in percutaneous cardiovascular intervention, are well described with regard to clinical efficacy and safety within a number of clinical studies. In vitro studies elucidating the correlation between coating additive and DCB performance are however rare but considered important for the understanding of DCB requirements and the improvement of established DCB. In this regard, we examined three different DCB-systems, which were developed in former studies based on the ionic liquid cetylpyridinium salicylate, the body-own hydrogel hyaluronic acid and the pharmaceutically well-established hydrogel polyvinylpyrrolidone, considering coating morphology, coating thickness, drug-loss, drug-transfer to the vessel wall, residual drug-concentration on the balloon surface and entire drug-load during simulated use in an in vitro vessel model. Moreover, we investigated particle release of the different DCB during simulated use and determined the influence of the three coatings on the mechanical behavior of the balloon catheter. We could show that coating characteristics can be indeed correlated with the performance of DCB. For instance, paclitaxel incorporation in the matrix can reduce the drug wash-off and benefit a high drug transfer. Additionally, a thin coating with a smooth surface and high but delayed solubility can reduce drug wash-off and decrease particle burden. As a result, we suggest that it is very important to characterize DCB in terms of mentioned properties in vitro in addition to their clinical efficacy in order to better understand their function and provide more data for the clinicians to improve the tool of DCB in coronary angioplasty.
The development of drug-eluting coatings based on hyaluronic acid (HA) is especially promising for implant-associated local drug delivery (LDD) systems, whose implantation provokes high insertion forces, as, for instance, cochlear implants or drug-coated balloons (DCB). The lubricious character of HA can then reduce the coefficient of friction and serve as drug reservoir simultaneously. In this context, we investigated several plasma- and wet-chemical methods for the deposition of HA-based coatings with LDD function on polyamide 12 as a model implant surface, conventionally used for DCB. In contrast to aminosilane, epoxy silane surface layers allowed the covalent attachment of a smooth and uniform HA base layer, which provided good adherence of further HA layers deposited by manual dip coating at a subsequent processing stage. The applied HA-crosslinking procedure during dip coating influences the transfer and release of paclitaxel, which could be reproducibly incorporated via infiltration. While crosslinking with N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride provided HA coatings on DCB, which allowed for an efficient paclitaxel transfer upon expansion in a vessel model, crosslinking with glutardialdehyde resulted in a slower drug release being more appropriate for implants with longer residence time in the body. The developed HA coating is hence well suited for spontaneous and sustained LDD.
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
OPEN ACCESSCoatings 2013, 3 254 efficient drug transfer of 49%, underlining the high potential of photochemically crosslinked PVP as a coating matrix for DCB.
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