Correlating Coating Characteristics with the Performance of Drug-Coated Balloons – A Comparative In Vitro Investigation of Own Established Hydrogel- and Ionic Liquid-Based Coating Matrices

Abstract

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.

Acute drug transfer and particle release of drug coated balloons within a porcine in-vitro model

“…It is therefore assumed that the overall number of particles would be even higher, if the DCB were additionally tracked through an in-vitro model. This thesis is supported by particle measurements by Kaule et al, that show 1.4 to 10.5 times higher number of particles ≥ 10 µm for Cetpyrsal-based DCB and HA-based DCB, respectively, were generated after track compared to the particles generated during the dilatation process [7]. Cetpyrsal-based DCB HA-based DCB SeQuent Please…”

“…Several studies dealt with the investigation of the drug transfer as well as particle release of different DCB in-vitro [5][6][7][13][14][15]. In-vitro drug transfer into a silicone mock vessel after the passage of a Cetpyrsal-based DCB through a track model is reported with 40 % of the initial balloon drug dose [5,7,14].…”

“…In-vitro drug transfer into a silicone mock vessel after the passage of a Cetpyrsal-based DCB through a track model is reported with 40 % of the initial balloon drug dose [5,7,14]. If results determined by Kaule et al are recalculated by referring the drug transfer to the initial load minus the drug loss during track, the recalculated drug transfer into the silicone tube was 55 % for the Cetpyrsaland 28 % for the HA-based DCB [7]. The drug transfer as determined with our porcine in-vitro model was 1.4 times or 2 times higher, respectively.…”

Drug-Eluting Balloons in the Treatment of Coronary De Novo Lesions: A Comprehensive Review

“…The coating of the balloon is important, as the coating should be physically able to maintain the drug on the balloon during transit to the lesion, thereby reducing wash off, while at the site of dilatation it should ensure a rapid and homogenous drug transfer to the vessel wall [16]. The coating differs with the contrast agent iopromide, the film-forming agent shellac, the amphiphilic butyryl trihexyl citrate, and urea being the most widely used.…”

Promising biocompatible hydrogels of crosslinked polyelectrolytes for biomedical applications

“…Hydrogels functionalised for drug delivery have a broad spectrum of application overarching drug eluting stent technology [1] and drug-coated balloons [2] for cardiovascular therapy but also injectable biomaterials [3] for ophthalmologic therapies [4], bone tissue engineering [5] and local cancer therapy [6].…”