scholarly journals Nanoparticles eluting stents for coronary intervention: Formulation, characterization and in vitro evaluation

2021 ◽  
Author(s):  
Ankit Agrawal ◽  
Ankur Raval ◽  
Shilpa Velhal ◽  
Vainav Patel ◽  
Vandana Patravale
Keyword(s):  
Smooth Muscle ◽  
Coronary Artery ◽  
Research Work ◽  
Coronary Intervention ◽  
Drug Formulation ◽  
Chromium Alloy ◽  
Residual Solvent ◽  
Drug Eluting ◽  
Nanoparticle Formulation

Coronary artery disease (CAD) is currently a leading cause of death worldwide. In the history of percutaneous coronary intervention for the treatment of CAD, a drug-eluting stent (DES) is recognized as a revolutionary technology that has the unique ability to significantly reduce restenosis and provide both mechanical and biological solutions simultaneously to the target lesion. The aim of the research work was to design and fabricate DES coated with a nanoparticulate drug formulation. Sirolimus, an inhibitor of the smooth muscle cell (SMC) proliferation and migration, was encapsulated in polymeric nanoparticles. The nanoparticle formulation was characterized for various physicochemical parameters. Cell viability and cell uptake studies were performed using human coronary artery smooth muscle cells (HCASMCs). The developed nanoparticle formulation showed enhanced efficacy compared to plain drug solution and exhibited time-dependent uptake into the HCASMCs. The developed nanoparticle formulation was coated on the FlexinniumTM ultra-thin cobalt-chromium alloy coronary stent platform. The nanoparticle coated stents were characterized for morphology and residual solvent analysis. In-vitro drug release was also evaluated. Ex-vivo arterial permeation was carried out to evaluate the nanoparticle uptake from the surface of the stents. The characterization studies together corroborated that the developed nanoparticle coated stent can be a promising replacement of the current drug-eluting stents.

scholarly journals Biosafety and Efficacy Evaluation of a Biodegradable Magnesium based Drug-eluting Stent in Porcine Coronary Artery

2020 ◽  
Author(s):  
Jinzhou Zhu ◽  
Xiyuan Zhang ◽  
Jialin Niu ◽  
Yongjuan Shi ◽  
Zhengbin Zhu ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Coronary Artery ◽  
Smooth Muscle Cells ◽  
Porcine Model ◽  
Muscle Cells ◽  
Comparable Efficacy ◽  
Drug Eluting Stent ◽  
Drug Eluting

Abstract Although drug-eluting stent (DES) has become the standard for percutaneous coronary interventions (PCI) based revascularization, stent thrombosis has emerged as a major cause of death and morbidity for those clinical commonly used permanent stents. Drug-eluting bioresorbable stent (BRS) was thus developed as an alternative to DES, which can be completely absorbed after its therapeutic period. Among them, magnesium (Mg) based BRS has attracted great attention due to its suitable mechanical properties, innovative chemical features and well-proven biocompatibility. In the present work, a Mg–Nd–Zn-Zr (JDBM) based drug-eluting BRS loaded with rapamycin was prepared, and its biosafety and efficacy for coronary artery stenosis were evaluated via in vitro and in vivo experiments. The smooth muscle cells adhesion of PDLLA/RAPA coated alloy and the rapamycin pharmacokinetics of JDBM BRS were first assessed in vitro. JDBM BRS and commercial DES Firehawk were then implanted in the coronary arteries of a porcine model. Neointimal hyperplasia was evaluated at 30, 90, and 180 days, and re-endothelialization was evaluated at 30 days. Furthermore, Micro-CT and optical coherence tomography (OCT) analysis were performed to evaluate the technical feasibility and biocompatibility of JDBM alloy based drug-eluting BRS in vivo. The results showed the inhibition ability of PDLLA/RAPA coated JDBM to smooth muscle cells adhesion and moderate drug release rate of JDBM BRS, demonstrating good anti-restenosis ability in vitro. In vivo, low local and systemic risks of JDBM alloy based BRS was demonstrated in the porcine model. We also showed that this novel BRS was associated with a comparable efficacy profile and high anti-restenosis performance. These findings may confer long term advantages for the use of this BRS over a traditional DES.

scholarly journals Biosafety and efficacy evaluation of a biodegradable magnesium-based drug-eluting stent in porcine coronary artery

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jinzhou Zhu ◽  
Xiyuan Zhang ◽  
Jialin Niu ◽  
Yongjuan Shi ◽  
Zhengbin Zhu ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Cell Adhesion ◽  
Coronary Artery ◽  
Smooth Muscle Cell ◽  
Degradation Rate ◽  
Porcine Model ◽  
Drug Eluting Stent ◽  
Drug Eluting

AbstractAlthough the drug-eluting stent (DES) has become the standard for percutaneous coronary intervention (PCI)-based revascularization, concerns remain regarding the use of DES, mainly due to its permanent rigid constraint to vessels. A drug-eluting bioresorbable stent (BRS) was thus developed as an alternative to DES, which can be absorbed entirely after its therapeutic period. Magnesium (Mg)-based BRSs have attracted a great deal of attention due to their suitable mechanical properties, innovative chemical features, and well-proven biocompatibility. However, the primary disadvantage of Mg-based BRSs is the rapid degradation rate, resulting in the early loss of structural support long before the recovery of vascular function. Recently, a new type of patented Mg–Nd–Zn-Zr alloy (JDBM) was developed at Shanghai Jiao Tong University to reduce the degradation rate compared to commercial Mg alloys. In the present investigation, a poly(d,l-lactic acid)-coated and rapamycin eluting (PDLLA/RAPA) JDBM BRS was prepared, and its biosafety and efficacy for coronary artery stenosis were evaluated via in vitro and in vivo experiments. The degree of smooth muscle cell adhesion to the PDLLA/RAPA coated alloy and the rapamycin pharmacokinetics of JDBM BRS were first assessed in vitro. JDBM BRS and commercial DES FIREHAWK were then implanted in the coronary arteries of a porcine model. Neointimal hyperplasia was evaluated at 30, 90, and 180 days, and re-endothelialization was evaluated at 30 days. Furthermore, Micro-CT and optical coherence tomography (OCT) analyses were performed 180 days after stent implantation to evaluate the technical feasibility, biocompatibility, and degradation characteristics of JDBM BRS in vivo. The results show the ability of a PDLLA/RAPA coated JDBM to inhibit smooth muscle cell adhesion and moderate the drug release rate of JDBM BRS in vitro. In vivo, low local and systemic risks of JDBM BRS were demonstrated in the porcine model, with preserved mechanical integrity after 6 months of implantation. We also showed that this novel BRS was associated with a similar efficacy profile compared with standard DES and high anti-restenosis performance. These findings may confer long term advantages for using this BRS over a traditional DES.

Unprotected Left Main Coronary Artery Percutaneous Coronary Intervention-Our Experiences at a Tertiary Hospital

2014 ◽  
Vol 6 (2) ◽  
pp. 107-111
Author(s):  
S Munwar ◽  
AHMW Islam ◽  
S Talukder ◽  
AQM Reza ◽  
T Ahmed ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Coronary Artery ◽  
Left Main Coronary Artery ◽  
Coronary Intervention ◽  
Drug Eluting Stent ◽  
Bare Metal ◽  
Coronary Artery Diseases ◽  
Left Main ◽  
Percutaneous Coronary ◽  
Drug Eluting

Background: Aim of the study was to evaluate the primary procedural success of percutaneous coronary intervention of unprotected left main coronary artery stenosis using either Bare-metal stents or drug eluting stent. Methods: Total 33 patients were enrolled in this very preliminary non-randomized prospective cohort study. Among them, Male: 25 and Female: 8. Total 35 stents were deployed. Mean age were for Male: 59 yrs, for Female: 62 yrs. Associated coronary artery diseases risk factors were dyslipidemia, High Blood pressure, Diabetes Mellitus, Positive family history for coronary artery diseases and smoking. Results: Among the study group; 26 (78%) were Dyslipidemic, 24(70%) were hypertensive; 17 (51.5%) patients were Diabetic, 11(33%) were smoker and 7(21%) patients had family history of Ischaemic heart disease. Female patients were more obese (BMI M 26: F 27) and developed coronary artery diseases in advance age. Common stented territory were left main: 20 (60%), Left main to left anterior descending artery 7 (22%) and Left main to left circumflex artery 6 (18%). Average length and diameter of stent was 3.5 and 18 mm respectively. Stent used: Bare Metal Stent 5 (15%), Drug Eluting Stent: 28 (85%). Among the different Drug Eluting Stents, Everolimus eluting stents were 11 (39.3%), Sirolimus eluting 10(35.7%), Paclitaxel eluting 3 (10.7%), Biolimus eluting 3 (10.7%) and Zotarolimus eluting1 (3.6%). In the present study, overall survival outcome was 94% (31 patient), mortality of cardiac cause 3% (1 patient) and 1 patient (3%) died of hepatocellular carcinoma. Conclusion: Our study has shown that percutaneous coronary intervention of the unprotected left main is a safe and effective alternative to Coronary Artery Bypass Graft (CABG). DOI: http://dx.doi.org/10.3329/cardio.v6i2.18349 Cardiovasc. j. 2014; 6(2): 107-111

scholarly journals Effect of Paclitaxel+Hirudin on the TLR4-MyD88 Signaling Pathway During Inflammatory Activation of Human Coronary Artery Smooth Muscle Cells and Mechanistic Analysis

2018 ◽  
Vol 50 (4) ◽  
pp. 1301-1317 ◽  
Author(s):  
Hongmei Li ◽  
Xian Wang ◽  
Anlong Xu
Keyword(s):  
Smooth Muscle ◽  
Coronary Artery ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Dependent Manner ◽  
Human Coronary Artery ◽  
Post Intervention ◽  
Inflammatory Activation ◽  
Myd88 Pathway

Background/Aims: Approximately 10%-20% of patients with acute cardiovascular disease who have received coronary intervention suffer restenosis and high inflammation. The stent compound paclitaxel+hirudin was prepared for the treatment of post-intervention restenosis. This study aimed to explore the anti-inflammatory and anti-restenosis mechanisms of paclitaxel+hirudin with regard to the TLR4/MyD88/NF-κB pathway. Methods: Human coronary artery smooth muscle cells (HCASMCs) at 4-6 generations after in vitro culture were used as a model. Lipopolysaccharide (LPS) was used as an inducer to maximally activate the TLR4/MyD88/NF-κB inflammation pathway. After MyD88 knockdown and selective blocking of MyD88 degradation with epoxomicin, the effects of paclitaxel+hirudin stenting on key sites of the TLR4/MyD88/NF-κB pathway were detected using ELISA, Q-PCR, and western blot analysis. Results: LPS at 1 μg/mL for 48 h was the optimal modeling condition for inflammatory activation of HCASMCs. Paclitaxel+hirudin inhibited the levels of key proteins and the gene expression, except for that of the MyD88 gene, of the TLR4-MyD88 pathway. The trend of the effect of paclitaxel+hirudin on the pathway proteins was similar to that of MyD88 knockdown. After epoxomicin intervention, the inhibitory effects of paclitaxel+hirudin on the key genes and proteins of the TLR4-MyD88 pathway were significantly weakened, which even reached pre-intervention levels. Paclitaxel+hirudin affected the MyD88 protein in a dosage-dependent manner. Conclusion: The paclitaxel+hirudin compound promotes MyD88 degradation in the TLR4/MyD88/NF-κB pathway to reduce the activity of TLR4 and NF-κB p65 and to weaken the LPS-initiated inflammatory reactions of IL-1β, IL-6, and TNF-α.

Dynamic kinking of right coronary artery after the button Bentall procedure

2021 ◽  
Vol 14 (1) ◽  
pp. e239128
Author(s):  
Tomoki Fukui ◽  
Nobuyuki Ogasawara ◽  
Shinji Hasegawa
Keyword(s):  
Coronary Artery ◽  
Right Coronary Artery ◽  
Multidetector Ct ◽  
Coronary Intervention ◽  
Drug Eluting Stent ◽  
Sinus Of Valsalva Aneurysm ◽  
Bentall Procedure ◽  
Percutaneous Coronary ◽  
Drug Eluting

Postoperative coronary artery complications after Bentall procedures are well recognised but are rare and potentially fatal. There have been only five cases documenting percutaneous coronary intervention (PCI) for right coronary artery (RCA) involvements after button Bentall procedures. We describe a case of postoperative silent myocardial ischaemia in a 72-year-old man who underwent the button Bentall procedure for a right sinus of Valsalva aneurysm. On postoperative day 15, an RCA complication was incidentally detected by follow-up multidetector CT. Coronary angiography showed proximal RCA kinking, which was not an anastomosis but a native coronary artery. The patient underwent a successful PCI with drug-eluting stent implantation. We reviewed six cases consisting of this case and five previous cases treated with PCI. These cases enhance the recognition of potential RCA complications after the button Bentall procedure.

Coronary smooth muscle reactivity to muscarinic stimulation after ischemia-reperfusion in porcine myocardial infarction

2003 ◽  
Vol 95 (1) ◽  
pp. 81-88 ◽  
Author(s):  
Antonio Rodríguez-Sinovas ◽  
Josep Bis ◽  
Inocencio Anivarro ◽  
Javier de la Torre ◽  
Antoni Bayés-Genís ◽  
...  
Keyword(s):  
Blood Flow ◽  
Smooth Muscle ◽  
Coronary Artery ◽  
Coronary Blood Flow ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Severe Left Ventricular Dysfunction ◽  
Coronary Smooth Muscle

This study tested whether ischemia-reperfusion alters coronary smooth muscle reactivity to vasoconstrictor stimuli such as those elicited by an adventitial stimulation with methacholine. In vitro studies were performed to assess the reactivity of endothelium-denuded infarct-related coronary arteries to methacholine ( n = 18). In addition, the vasoconstrictor effects of adventitial application of methacholine to left anterior descending (LAD) coronary artery was assessed in vivo in pigs submitted to 2 h of LAD occlusion followed by reperfusion ( n = 12), LAD deendothelization ( n = 11), or a sham operation ( n = 6). Endothelial-dependent vasodilator capacity of infarct-related LAD was assessed by intracoronary injection of bradykinin ( n = 13). In vitro, smooth muscle reactivity to methacholine was unaffected by ischemia-reperfusion. In vivo, baseline methacholine administration induced a transient and reversible drop in coronary blood flow (9.6 ± 4.6 to 1.9 ± 2.6 ml/min, P < 0.01), accompanied by severe left ventricular dysfunction. After ischemia-reperfusion, methacholine induced a prolonged and severe coronary blood flow drop (9.7 ± 7.0 to 3.4 ± 3.9 ml/min), with a significant delay in recovery ( P < 0.001). Endothelial denudation mimics in part the effects of methacholine after ischemia-reperfusion, and intracoronary bradykinin confirmed the existence of endothelial dysfunction. Infarct-related epicardial coronary artery shows a delayed recovery after vasoconstrictor stimuli, because of appropriate smooth muscle reactivity and impairment of endothelial-dependent vasodilator capacity.

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