Common anti-restenotic drug for DCB is Paclitaxel. Some of advantages of paclitaxel are: 1) It is a very hydrophobic small molecule which allows rapid vessel uptake 2) Simple excipient coatings can be used such as molecular spacers like contrast agent 3) It is a stable molecule in tissue with lasting effects from a single dose. However, paclitaxel modifications (crystalline form) mean coating integrity and transfer are variable with substantial portion lost downstream into blood and tissue. Loss of paclitaxel into body remains a significant safety concern. Larger particulate sizes created from crystalline coating formulations have been shown to be associated with Slow Flow phenomenon (1) and potentially delayed healing & higher amputation rates (2). Sirolimus (Rapamycin; immunosuppressant) is an antiproliferative & anti-inflammatory cytostatic agent, originally used in transplant patients to avoid rejection. Sirolimus is the standard for coronary artery disease treatment via Drug-eluting stents (DES) and has proven to be safe and effective in large number of patients. It offers wide therapeutic range and lower risk of dose-dependent toxicity. However, unlike the stability of paclitaxel, Sirolimus has an elimination half-life of ~ 60hrs, thus, some method of "topping up" sirolimus levels would be needed during the period of the restenotic cascade (up to 9 mo in PAD) to obtain long term clinical effectiveness. Also, Sirolimus is a bigger molecule than paclitaxel, thus, to optimize drug uptake a more advanced coating is required with incorporation of a an "absorption enhancer" in the coating to achieve best results when applying a lower effective dose of drug to the balloon SELUTION SLR (MedAlliance MA, Nyon, Switzerland) is a novel CE-marked drug-coated balloon incorporating non-crystalline sirolimus embedded in biodegradable polymer micro-reservoirs, providing sustained sirolimus release out to 90 days and allowing for low drug dose of 1 µg/mm2. Bench test data have previously shown that particulates generated are much smaller and more homogenous compared to the paclitaxel coated balloons.

A preclinical study was performed in large animal models (porcine) to assess the potential downstream emboli for the SELUTION SLR in Peripheral and Coronary vascular beds Multiple balloons were deployed at target sites to achieve equivalent of max dose per indication: Peripheral: 7 mm x 200 mm, Coronary: 4.5mm x 40 mm. Histopathology was further assessed at treatment site and downstream tissue beds and major organs. Skeletal muscle and coronary band for potential embolic changes were assessed in addition to Distal paclitaxel concentration. Histology assessment was performed to look for distal embolization.

Regardless of the vascular bed, no vascular injury related to downstream embolization was observed. There was an absence of thrombus or crystalline emboli downstream. Vessels were normal microscopically and there was no histopathological or micromorphological changes at the treatment site.

The Novel Sirolimus eluting SELUTION SLR balloon showed no distal embolization, and histopathological changes at site of treatment or in non-target downstream organs. The results are further confirmed by the absence of slow-flow phenomenon after deployment of this balloon in clinical applications (1). First in man clinical study has been completed with 2-year data available and several clinical studies with this technology for treatment of PAD are ongoing.

1) Tang TY, Sulaiman MSB, Soon SXY, Yap CJQ, Patel A, Chong TT. Slow-flow phenomena following lower limb paclitaxel- and sirolimus-coated balloon angioplasty in the setting of chronic limb threatening ischaemia—a case series. Quant Imaging Med Surg 2022;12(3):2058-2065. doi: 10.21037/qims-21-633 2) Tokuda et al., Incidence and clinical outcomes of the slow-flow phenomenon after infrapopliteal balloon angioplasty Journal of Vascular Surgery 2017 651047-1054. DOI: (10.1016/j.jvs.2016.08.118)