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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.

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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.

Drug-coated balloon catheters are a novel clinical treatment alternative for coronary and peripheral artery diseases. Calcium alginate, poly(vinylethylimidazolium bromide) and polyacrylamide hydrogels were used as vessel models in this in vitro study. In comparison to a simple silicone tube their properties can be easily modified simulating different types of tissue. Local drug delivery after balloon dilation in the first crucial minute was determined in a vessel-simulating flow-through cell by a simulated blood stream.Balloon catheters were coated with paclitaxel using the ionic liquid cetylpyridinium salicylate as a novel carrier. Drug transfer from coated balloon catheters to different simulated vessel walls was evaluated and compared to a silicone tube. The highest paclitaxel delivery upon dilation was achieved with calcium alginate as the vessel model (60%) compared to polyacrylamide with 20% drug transfer. The silicone tube showed the least amount of wash-off (<1%) by a simulated blood stream after one minute from the vessel wall. The vessel-simulating flow-through cell was combined with a model coronary artery pathway to estimate drug loss during simulated use in an in vitro model. Calcium alginate and polyacrylamide hydrogels were used as tissue models for the simulated anatomic implantation process.In both cases, similar transfer rates for paclitaxel upon dilation were detected.