A novel nanocarrier sirolimus-coated balloon for coronary interventions: 12-Month data from the Nanoluté Registry.

BACKGROUND: The aim of the Nanoluté registry was to observe the clinical performance of a novel sirolimus coated balloon (SCB) (Concept Medical Research Private Limited, India) for the treatment of coronary de-novo and restenotic lesions. METHODS: All patients treated with SCB between July 2012 and September 2015 were enrolled at Indian centres and clinically followed for 1, 3, 6 and 12 months post-procedure. Primary endpoints were procedural success and device-oriented adverse cardiac events (DOCE) at 12 months. DOCE were defined as a composite of cardiac death, target lesion revascularization (TLR) and target vessel-myocardial infarction. RESULTS: A total of 394 SCB were used in 332 patients to treat 356 lesions. In-stent restenosis and small coronary vessel disease occurred in 46% and 43% of the patients respectively. Mean balloon length and diameter (average ±â€¯SD) were 21.83 ±â€¯6.70 mm and 2.69 ±â€¯0.45 mm respectively. All patients with 1 year follow-up were included. Overall DOCE rate was 4.2% (n = 14) which included death 0.3% (n = 1), TLR 3.6% (n = 12) and myocardial infarction 0.3% (n = 1). CONCLUSION: The Nanoluté prospective registry, is the first clinical evidence of the safety and feasibility of this type of SCB, both in patients with in-stent restenosis or de novo lesions.

Merging the properties of a sirolimus coated balloon with those of a bioresorbable polymer sirolimus eluting stent to address the "diabetes issue". Results from the En-Abl multicenter registry.

BACKGROUND: Patients with diabetes mellitus (DM) have poorer outcomes after percutaneous coronary intervention than patients without diabetes. The Abluminus DES+™ drug-eluting stent (DES) features a novel technology of fusion coating of PLLA bioresorbable polymer on both the abluminal surface of the stent and exposed parts of the balloon. The aim of this study was to evaluate the efficacy/safety profile of the Abluminus DES+ in an all-comers population with minimal exclusion criteria and with a specific focus on diabetic patients. METHODS: Multicenter, prospective, all-comers registry performed in 31 centers in India. Patients were analyzed according to the diagnosis of DM and insulin dependency (ID or Non ID): non-DM (1256 patients), NIDDM (498 patients), IDDM (99 patients). The primary endpoint was a composite of device-oriented major adverse cardiac events (MACE): cardiac death, target vessel-related myocardial infarction (MI), and ischemia-driven target lesion revascularization (TLR)/ target vessel revascularization (TVR) at 1 year. Stent thrombosis (ST) at any time point was also recorded. RESULTS: The MACE rate at 1 year in the overall population was 2.3% and it was mainly driven by a 1.57% rate of TLR/TVR. Although patients with IDDM showed slightly higher figures for MACE (non-DM 2.3%, NIDDM 2.8%, IDDM 4%, P=0.09), as well as for single end-points, none of them reached statistical significance. The rate of ST was 0.56%, 0.4%, 1% for non-DM, NIDDM and IDDM group, respectively (P=0.6). CONCLUSIONS: The performance of the Abluminus DES+ is consistent among patients with or without diabetes, regardless the insulin dependency.

Biological effect on restenosis and vascular healing of encapsulated paclitaxel nanocrystals delivered via coated balloon technology in the familial hypercholesterolaemic swine model of in-stent restenosis.

AIMS: The aim of this study was to evaluate the biological efficacy of a novel lower-dose (2.5 µg/mm2) encapsulated paclitaxel nanocrystal-coated balloon (Nano-PCB) in the familial hypercholesterolaemic swine (FHS) model of iliofemoral in-stent restenosis. METHODS AND RESULTS: Nano-PCB pharmacokinetics were assessed in 20 femoral arteries (domestic swine). Biological efficacy was evaluated in ten FHS: 14 days following bare metal stent implantation each stent segment was randomised to a clinically available PCB (IN.PACT, n=14), the Nano-PCB (n=14) or an uncoated balloon (n=12). Angiographic, optical coherence tomography and histological evaluation was performed at 28 days after treatment. Arterial paclitaxel concentration was 120.7 ng/mg at one hour and 7.65 ng/mg of tissue at 28 days with the Nano-PCB. Compared to the control uncoated group, both PCBs significantly reduced percent area stenosis (Nano-PCB: 36.0±14.2%, IN.PACT: 29.3±9.2% vs control: 67.9±15.1%, p<0.001). Neointimal distribution in the entire stent length was more homogenous in the Nano-PCB. Histological evaluation showed comparable degrees of neointimal proliferation in both PCBs; however, the Nano-PCB showed slightly higher levels of neointimal maturity and endothelialisation. CONCLUSIONS: Lower-dose encapsulated paclitaxel nanocrystals delivered via a coated balloon displayed comparable biological efficacy with superior healing features compared to a clinically validated PCB technology.

Unprotected distal left main bifurcation drug eluting stent restenosis: first successful experience with simultaneous kissing balloon dilatation using sirolimus coated balloon.

Treatment of unprotected left main (ULM) in-stent restenosis (ISR) in patients with prior drug eluting stent implantation is challenging. Treatment usually involves complex stenting procedures or bypass grafting. Drug coated balloon (DCB) is relatively new concept which is usually used in treatment of ISR. In a patient of ULM ISR, use of DCBs is a safe, economic and a technically simple option with relatively good outcomes. We report use of simultaneous kissing balloon dilatation with novel sirolimus coated balloons (SCBs) via radial artery to treat ULM ISR.

Preclinical evaluation of a novel abluminal surface coated sirolimus eluting stent with biodegradable polymer matrix.

BACKGROUND: Second generation of drug eluting stents (DES) has attempted to improve safety using abluminal sirolimus drug delivery with biodegradable polymers matrix. The present preclinical study was designed to investigate the safety and efficacy profile of Abluminus™ stents (SES). This is a new coronary stent with sirolimus and biodegradable polymer matrix coated on abluminal stent and balloon surface. METHODS: SES were compared with two controls: bare metal stent (BMS) and BMS + polymer coated stents (PC). All devices (40 stents) were implanted in porcine coronary arteries with primary endpoint of endothelialization at 7 days and subsequent histological and morphometric evaluations at 7, 30 and 90 days. RESULTS: Early endothelialization at seven days was complete in all stents. Histology at 30 days revealed minimum inflammation in all groups and increased at 90 days in PC group while it was absent at 180 days. Thirty day morphometry showed significantly reduction of neointimal area in Abluminus™ (SES 0.96±0.48 mm(2); BMS 1.83±0.34 mm(2); PC 1.76±0.55 mm(2); P<0.05); after 90 days neointimal area was 1.10±0.54 mm(2) for SES; 1.92±0.36 mm(2) for BMS; and 1.94±0.48 mm(2) for PC; P<0.05). Neointimal thickness at 30 and 90 days respectively was 0.15±0.07 and 0.18±0.10 mm for SES, 0.57±0.08 and 0.61±0.09 mm for BMS and 0.52±0.09 and 0.59±0.08 mm, P<0.001 for PC group. CONCLUSIONS: The most significant experimental evidence appears to be earlier endothelialization at 7 days for SES which led to safety of the device. Efficacy of the device was also observed by a reduced neointimal thickness and minimized inflammatory score at all follow-ups. Termination of antiplatelet at 30 days has not shown any further complications. Polymer thickness was almost in negligible amount at 180 days with no inflammation.

A new polymer-free drug-eluting stent with nanocarriers eluting sirolimus from stent-plus-balloon compared with bare-metal stent and with biolimus A9 eluting stent in porcine coronary arteries.

BACKGROUND: Permanent polymers in first generation drug-eluting stent (DES) have been imputed to be a possible cause of persistent inflammation, remodeling, malapposition and late stent thrombosis. We aim to describe the in vivo experimental result of a new polymer-free DES eluting sirolimus from stent-plus-balloon (Focus np stent, Envision Scientific) compared with a bare-metal stent (BMS) (Amazonia CroCo, Minvasys) and with a biolimus A9 eluting stent (Biomatrix, Biosensors). METHODS: In 10 juvenile pigs, 23 coronary stents were implanted in the coronary arteries (8 Amazonia CroCo, 8 Focus np, and 7 Biomatrix). At 28-day follow-up, optical coherence tomography (OCT) and histology were used to evaluate neointimal hyperplasia and healing response. RESULTS: According to OCT analysis, Focus np stents had a greater lumen area and less neointimal hyperplasia response than BMS and Biomatrix had. Histomorphometry results showed less neointimal hyperplasia in Focus np than in BMS. Histology showed a higher fibrin deposition in Biomatrix stent compared to Focus np and BMS. CONCLUSIONS: The new polymer-free DES with sirolimus eluted from stent-plus-balloon demonstrated safety and reduced neointimal proliferation compared with the BMS and Biomatrix stents at 28-day follow-up in this porcine coronary model. This new polymer-free DES is promising and warrants further clinical studies.

Emerging technologies: polymer-free phospholipid encapsulated sirolimus nanocarriers for the controlled release of drug from a stent-plus-balloon or a stand-alone balloon catheter.

Drug-eluting stents have proven to be effective in reducing the risk of late restenosis. In order to achieve a controlled and prolonged release of the antiproliferative agent, current drug-eluting stents utilise various biodegradable as well as non-erodible polymeric blends to coat the stent surface and to serve as drug carriers. The utilisation of polymeric compounds in current drug-eluting stents may eventually limit their performance as well as their clinical applicability due to the potential induction of undesirable local reactions. The development of alternative, polymer-free drug carriers has the potential to overcome some of the limitations of current drug-eluting stent formulations. Moreover, improvements in drug carriers may also result in an expansion of the technological possibilities for other intravascular drug delivery systems, such as metal-free or even implant-free solutions. This article describes the structure and the preclinical validation profile of a novel phospholipid encapsulated sirolimus nanocarrier, used as a coating in two formulations: a coronary stent-plus-balloon system and a stand-alone balloon catheter. The nanoparticles provided a stable, even and homogenous coating to the devices in both formulations. Dose-finding studies allowed the most appropriate identification of the best nanoparticle structure associated with an extremely efficient transfer of drug to all layers of the vessel wall, achieving high tissue concentrations that persisted days after the application, with low systemic drug leaks.

Estudo da dose excipiente: fármaco com avaliação da hiperplasia neointimal por tomografia de coerência óptica e histopatologia em artérias coronárias porcinas após o emprego do balão eluidor de sirolimus / Excipient: Drug Dose Finding with Neointimal Hyperplasia Assessed by Optical Coherence Tomography and Histopathology in Porcine Coronary Arteries after Sirolimus-Eluting Balloon Employment

Introdução: Magic TouchTM é um balão recoberto com nanopartículas carreadoras de sirolimus. Objetivamos encontrar a dose excipiente: fármaco com a maior capacidade de inibição da proliferação neointimal 28 dias após o uso desse balão pós-implante de stent não-farmacológico em artérias coronárias porcinas. Métodos: Foram avaliados 14 porcos com implante coronário de stent não-farmacológico seguido por dilatação(60 segundos) com balões com relação excipiente: sirolimus 1:1, 0,5:1, 0,25:1 e 1:0 ou balão controle. Após 28 dias a hiperplasia neointimal foi estudada por tomografia de coerência óptica e histopatologia. Resultados: A hiperplasia neointimal porcentual (%) avaliada pela tomografia de coerência óptica e pela histomorfometria foi de 32,2 e 35,1, 28,1 e 33,4, 17,3 e20,9, 28,6 e 30,2, e 37,9 e 42,3 nos grupos excipiente: sirolimus 0,25:1, 0,5:1, 1:1, 1:0 e balão controle, respectivamente (P = 0,03 para excipiente: sirolimus 1:1 vs. balão controle). A espessura (mm) da neoíntima inter-hastes foi de 0,23, 0,30, 0,16, 0,24 e 0,30 nos grupos excipiente: sirolimus 0,25:1,0,5:1, 1:1, 1:0 e balão controle, respectivamente (P < 0,01para excipiente: sirolimus 1:1 vs. balão controle). Os escores de inflamação, injúria e deposição de fibrina foram baixos e sem diferenças significantes entre os grupos. Conclusões: Ocorreu gradual aumento da eficácia inibitória da proliferação neointimal à medida que a concentração do excipiente aumentou; amenor eficácia ocorreu com a formulação excipiente: sirolimus 0,25:1 e a mais intensa inibição foi observada com a formulação excipiente: sirolimus 1:1, a qual reduziu significantemente a proliferação neointimal em comparação com o grupo controle, com baixos índices de inflamação e injúria.