Novel Sirolimus–Coated Balloon Catheter

Abstract

Background-Limus-eluting stents are dominating coronary interventions, although paclitaxel is the only drug on balloon catheters with proven inhibition of restenosis. Neointimal inhibition by limus-coated balloons has been shown in few animal studies, but data from randomized clinical trials are not available. The aim of the present preclinical studies was to achieve high and persistent sirolimus levels in the vessel wall after administration by a coated balloon. Methods and Results-Different coating formulations and doses were studied in the porcine coronary model to investigate sirolimus tissue levels at different time points as well as efficacy at 1 month using quantitative coronary angiography and histomorphometry. Loss of the selected coating in the valve, guiding catheter, and blood was low (2±14% of dose). Acute drug transfer to the vessel wall was 14.4±4.6% with the crystalline coating, whereas the amorphous coatings were less effective in this respect. Persistence of sirolimus in the vessel wall until 1 month was 40% to 50% of the transferred drug. At 1-month follow-up, a modest but significant reduction of neointimal growth was demonstrated in a dose range from 4 μg/mm 2 to 2×7 μg/mm 2 , for example, maximum neointimal thickness of 0.38±0.13 versus 0.65±0.21 mm in the uncoated control group. Conclusions-Various Methods Research StrategyA variety of sirolimus balloon-coating formulations were prepared and tested with the primary aim of achieving high transfer rates to the arterial wall and long-lasting persistence in the vessel wall because of increased crystal formation. Other important properties were minimal loss of the drug on the way to the treatment site, inhibition of injury-induced neointimal proliferation, and good local and systemic tolerance. Materials and Coating of BalloonsConventional percutaneous transluminal coronary angioplasty balloon catheters (SeQuent [Neo], B. Braun Melsungen AG, Berlin, Germany) were coated using different coating formulations, coating procedures, and dosages (Table 1; Figure 1). Sirolimus was produced according to Good Manufacturing Practice by Euticals S.p.A., Site of Rozzano, Italy; solvents were USP or analytic grade. Coating was performed in a dose range of ≤7-μg sirolimus per mm 2 balloon surface by dispersing a precisely defined volume of organic solvents containing sirolimus with different matrix-forming additives on the balloons.The different coating procedures resulted in different physicochemical properties in terms of amorphous and crystalline characteristics.After coating, the catheters were left to dry for at least 24 hours at room temperature before use or further processing. For some of the experiments, bare stainless steel stents (B. Braun AG, Melsungen. Germany) were mounted onto balloons using a hand crimper HH100-101 (Machine Solutions, Flagstaff, AZ). Balloon catheters used for determination of sirolimus loss in blood on the way to the coronary artery were left without stents. Balloon catheters used for the animal studies were EO sterilized b...

Linear Micro-patterned Drug Eluting Balloon (LMDEB) for Enhanced Endovascular Drug Delivery

“…DEB technologies have evolved rapidly by developing coating formulations or surface modification of DEBs for enhanced drug delivery. In addition, new drugs such as sirolimus or zotarolimus were introduced and their improved bioavailability and efficacy were demonstrated 26 , 27 . Different types of drug formulations to coat such limus-family drugs have also been developed using biodegradable polymer or nanoparticles 28 – 30 .…”

Drug-coated balloon treatment in coronary artery disease: Recommendations from an Asia-Pacific Consensus Group

“…Most recent researches have focused on different coatings and drug delivery technologies. Although zotarolimus-and sirolimus-DCB have shown promising results in preclinical studies, it remains to be determined whether they will result in relevant clinical effects [76][77][78]. In comparison to zotarolimus-eluting stents, zotarolimus-coated balloons demonstrated similar reductions in neointimal proliferation with a reduction in inflammation scores [77].…”

Safety Issues Associated with Paclitaxel-Eluting Balloons and Progress of Sirolimus-Eluting Balloons

“…The sequent please paclitaxel-coated balloon was the first and most widely used deb in cad. A novel sequent sirolimus deb was fabricated with a drug concentration of 4 µg/mm2 (figure 3) [32]. A randomized, multicenter trial enrolling 50 patients has been proposed to compare safety and efficacy [33].…”