Understudied factors in drug‐coated balloon design and evaluation: A biophysical perspective

Abstract

Drug‐coated balloon (DCB) percutaneous interventional therapy allows for durable reopening of the narrowed lumen via physical tissue expansion and local anti‐restenosis drug delivery, providing an alternative to traditional uncoated balloons or a permanent indwelling implant such as a conventional metallic drug‐eluting stent. While DCB‐based treatment of peripheral arterial disease (PAD) has been incorporated into clinical guidelines, DCB use has been recently curtailed due to reports that showed evidence of increased mortality risk in patients treated with paclitaxel (PTX)‐coated balloons. Given the United States Food and Drug Administration's 2019 consequent warning regarding PTX‐eluting DCBs and the subsequent marked reduction in clinical DCB use, there is now a critical need to better understand the compositional and mechanical factors underlying DCB efficacy and safety. Most work to date on DCB refinement has focused on designing both the enabling balloon catheter and alternate coatings composed of various drugs and excipients, followed by device evaluation in preclinical and clinical studies. We contend that improvement in DCB performance will require a better understanding of the biophysical factors operative during and following balloon deployment, and moreover that the elaboration and demonstrated control of these factors are needed to address current concerns with DCB use. This article provides a perspective on the biophysical interactions that govern DCB performance and offers new design strategies for the development of next‐generation DCB devices.

Choosing the right treatment for the right lesion, Part II: a narrative review of drug-coated balloon angioplasty and its evolving role in dialysis access maintenance

“…In the subsequent decade, numerous RCTs and additional studies have been published regarding their use in AV access, however, their efficacy in this area has been less pronounced than in that of CAD and PAD, as will be Search terms used MeSH: "dialysis" OR "hemodialysis" OR "arteriovenous fistula" AND "angioplasty" Non-MeSH: "drug" OR "eluting" OR "coated" OR "paclitaxel" AND "random" OR "randomized" discussed in later sections. All DCBs approved by the US Food and Drug Administration (FDA) for use in AV access at the time of this review's publication, and all that will be discussed in the following sections, contain paclitaxel as the drug component, and paclitaxel-coated balloons will simply be referred to as drug-coated balloons or "DCBs" in the subsequent sections (48).…”

“…It is important to note that current balloon components are not designed as high-pressure balloons (HPBs) and are not designed to primarily perform highquality angioplasty on stenotic AV access lesions-rather, DCBs should be thought of as complementary to successful POBA (43). DCBs are typically compliant, non-HPBs, with nominal inflation pressures on the order of 5-8 atmospheres (atm) and burst pressures 12-14 atm for the most commonly studied DCBs in AV access (43,48). AV access stenoses often require pressures in excess of 20 atm to efface the lesion waist, greater than the DCB is able to produce (52)(53)(54)(55).…”

“…Pre-dilation serves multiple purposes-it modifies the target lesion in a traumatic fashion, which may allow for better drug delivery to deeper vessel wall layers through intimal tears and other traumatic injuries, it facilitates complete DCB expansion, and it promotes maximal DCB surface contact with the vessel wall (48,67). The majority of evidence for the above has come from literature regarding DCB use in atherosclerotic arterial disease, however, the same principles likely hold true in the treatment of AV access stenosis (68)(69)(70).…”

“…The dose of paclitaxel loaded onto the balloon must account for the various inefficiencies in drug transfer, adhesion, and absorption, and must ultimately ensure a therapeutic dose is delivered. Despite the implementation of various drug-excipient combinations, the amount of drug delivered to the target vessel is only a small fraction of the total dose loaded onto the balloon, typically in the range of 10–15%, with the remainder lost to the systemic circulation or remaining on the balloon ( 32 , 48 ). Following delivery, there is some degree of washout that occurs, as not all of the delivered paclitaxel will remain adherent to the vessel wall or be absorbed into the underlying vessel layers ( 32 , 42 ).…”

“…While this high loading dose is needed to offset the amount of drug lost to inefficient vessel wall delivery and washout, the total systemic dose remains much smaller than that which is delivered systemically in oncologic uses, which may be up to 200–300 times that found on a DCB ( 40 , 43 ). Regardless, any degree of systemic drug release is undesirable, potentially resulting in off-target drug accumulation and harm, and the current degree of delivery inefficiency is a limitation of available DCBs ( 48 ).…”