scholarly journals Mutual influence of incorporated drugs in a dual drug delivery coating for cardiovascular applications

2017 ◽  
Vol 3 (2) ◽  
pp. 379-382
Author(s):  
Katharina Wulf ◽  
Michael Teske ◽  
Claudia Matschegewski ◽  
Daniela Arbeiter ◽  
Thomas Eickner ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Mutual Influence ◽  
Local Drug Delivery ◽  
Drug Eluting Stent ◽  
Vascular Endothelial ◽  
Effective Inhibition ◽  
Drug Eluting ◽  
The Stability ◽  
Endothelial Growth Factor

AbstractFor a long-term efficient drug-eluting stent for vascular applications, the development of drug-loaded coating, combining the effective inhibition of smooth muscle cell proliferation while promoting the re-endothelialization, is a promising concept. However the mostly required simultaneous incorporation of drugs can influence decisively the stability, efficacy and release of the respective drug. Therefore, the mutual influence of a dual local drug delivery coatings based on poly(L-lactide-co-ε-caprolactone) (PLLA-co-CL) containing vascular endothelial growth factor (VEGF165) coupled to the surface and an embedded drug, such as fluorescein diacetate (FDAc) instead of Paclitaxel (PTX) on the in vitro drug release was investigated. Surprisingly, for the investigated coating the immobilized VEGF loading was enhanced and the release profile was accelerated by FDAc incorporation. Even a manifold increase for the in vitro released amounts of VEGF was detected. In contrast, the immobilization of VEGF seems to have a negligible influence on the in vitro FDAc release profiles.

Neointima Inhibition: Comparison of Effectiveness of Non–Stent-based Local Drug Delivery and a Drug-eluting Stent in Porcine Coronary Arteries

Radiology ◽  
2006 ◽  
Vol 240 (2) ◽  
pp. 411-418 ◽  
Author(s):  
Ulrich Speck ◽  
Bruno Scheller ◽  
Claudia Abramjuk ◽  
Christoph Breitwieser ◽  
Juergen Dobberstein ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Coronary Arteries ◽  
Local Drug Delivery ◽  
Drug Eluting Stent ◽  
Drug Eluting ◽  
Comparison Of Effectiveness

scholarly journals Hierarchical Capillary Coating to Biofunctionlize Drug-Eluting Stent for Improving Endothelium Regeneration

Research ◽  
2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Jing Wang ◽  
Yunfan Xue ◽  
Jun Liu ◽  
Mi Hu ◽  
He Zhang ◽  
...  
Keyword(s):  
Real Time ◽  
Medical Devices ◽  
Drug Eluting Stent ◽  
Vascular Endothelial ◽  
Competitive Growth ◽  
Capillary Coating ◽  
Stent Restenosis ◽  
Solid Region ◽  
Drug Eluting ◽  
Endothelial Growth Factor

The drug-eluting stent (DES) has become one of the most successful and important medical devices for coronary heart disease, but yet suffers from insufficient endothelial cell (EC) growth and intima repair, eventually leading to treatment failure. Although biomacromolecules such as vascular endothelial growth factor (VEGF) would be promising to promote the intima regeneration, combining hydrophilic and vulnerable biomacromolecules with hydrophobic drugs as well as preserving the bioactivity after harsh treatments pose a huge challenge. Here, we report on a design of hierarchical capillary coating, which composes a base solid region and a top microporous region for incorporating rapamycin and VEGF, respectively. The top spongy region can guarantee the efficient, safe, and controllable loading of VEGF up to 1 μg/cm2 in 1 minute, providing a distinctive real-time loading capacity for saving the bioactivity. Based on this, we demonstrate that our rapamycin-VEGF hierarchical coating impressively promoted the competitive growth of endothelial cells over smooth muscle cells (ratio of EC/SMC~25) while relieving the adverse impact of rapamycin to ECs. We further conducted the real-time loading of VEGF on stents and demonstrate that the hierarchical combination of rapamycin and VEGF showed remarkable endothelium regeneration while maintaining a very low level of in-stent restenosis. This work paves an avenue for the combination of both hydrophobic and hydrophilic functional molecules, which should benefit the next generation of DES and may extend applications to diversified combination medical devices.

Abstract 13044: Serum Vascular Endothelial Growth Factor-C Levels are Inversely Associated with the Risk of Cardiac and Cerebrovascular Events Following Drug-eluting Stent Implantation

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Takashi Unoki ◽  
Hiromichi Wada ◽  
Masaharu Akao ◽  
Shuichi Ura ◽  
Akira Yamada ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Drug Eluting Stent ◽  
Vascular Endothelial ◽  
Cox Proportional Hazard ◽  
Cerebrovascular Events ◽  
Drug Eluting ◽  
Factor C ◽  
Endothelial Growth Factor

Background: Vascular endothelial growth factor-C (VEGF-C) plays a key role in lymphangiogenesis. Recently, we demonstrated that VEGF-C is closely associated with dyslipidemia and atherosclerosis. However, the prognostic value of VEGF-C levels after drug-eluting stent (DES) implantation is unknown. Methods and Results: We performed a prospective cohort study involving a total of 443 patients (age, 71.7±9.0 y [SD]; male, 73.8%; number of lesions, 1.6±0.8) who underwent successful DES implantation. Patients were recruited between January 2010 and October 2013, and were followed up over 3 years. The primary outcome was major adverse cardiac and cerebrovascular events (MACCE) defined as cardiovascular death, hospitalization due to acute coronary syndrome, stroke, heart failure, and coronary revascularization. The median follow-up was 617 (inter-quartile range, 320-937) days. Pre-procedural serum levels of high-sensitivity C-reactive protein (hsCRP), vascular endothelial growth factor-A (VEGF-A), and VEGF-C were measured. During the follow-up period, MACCE developed in a total of 106 patients (23.9%). Patients were divided into two groups based on the median of each biomarker. In Kaplan-Meier analyses, low-VEGF-C (P=0.0005 by log-rank test), but not high-hsCRP (P=0.3) or high-VEGF-A (P=0.3), was significantly associated with the risk of MACCE. Multivariate Cox proportional hazard analyses revealed that levels of VEGF-C (hazard ratio [HR], 0.77 per 1-SD increase; 95% confidence interval [CI], 0.62-0.94; P=0.011), but not hsCRP (HR, 1.05; 95% CI, 0.86-1.25; P=0.6) or VEGF-A (HR, 1.04; 95% CI, 0.86-1.23; P=0.6), were inversely and significantly associated with MACCE after adjustment for age, gender, and established risk factors, the number of lesions, and type of DES. Finally, we performed stepwise multivariate Cox proportional hazard analysis including data on age, gender, established risk factors, the number of lesions, type of DES, and VEGF-C levels. Notably, the only independent predictor of MACCE was the VEGF-C level (HR, 0.74 per 1-SD increase; 95% CI, 0.61-0.91; P=0.0042), followed by diabetes (HR, 1.47; 95% CI, 0.98-2.21; P=0.060). Conclusions: A low VEGF-C value may serve as a predictor of MACCE after DES implantation.

scholarly journals Local drug-delivery balloon for proliferative occlusive in-stent restenosis after drug-eluting stent

2011 ◽  
Vol 8 (1) ◽  
pp. 65-66
Author(s):  
Rigatelli Gianluca ◽  
Cardaioli Paolo ◽  
Dell’Avvocata Fabio ◽  
Giordan Massimo
Keyword(s):  
Drug Delivery ◽  
Local Drug Delivery ◽  
Drug Eluting Stent ◽  
Stent Restenosis ◽  
Drug Eluting ◽  
In Stent Restenosis

Abstract 17849: Serum Vascular Endothelial Growth Factor Levels Associated With the Risk of Major Adverse Cardiac and Cerebrovascular Events After Drug-eluting Stent Implantation

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Takashi Unoki ◽  
Daisuke Takagi ◽  
Kensuke Takabayashi ◽  
Suichi Ura ◽  
Akira Yamada ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Drug Eluting Stent ◽  
Vascular Endothelial ◽  
Proportional Hazard ◽  
Coronary Syndrome ◽  
Cox Proportional Hazard ◽  
Cerebrovascular Events ◽  
Drug Eluting ◽  
Endothelial Growth Factor

Background: Vascular endothelial growth factor (VEGF), a central player in angiogenesis, is not only involved in the progression of atherosclerotic plaque, but also required for preventing decompensated heart failure (HF). High circulating oxidatively modified LDL-cholesterol (oxLDL) levels are associated with vulnerability to the rupture of atherosclerotic lesions. However, the relationships of circulating VEGF and oxLDLs with major adverse cardiac and cerebrovascular events (MACCE) in patients undergoing coronary drug-eluting stent (DES) implantation are unclear. Methods and Results: We enrolled 441 patients who electively underwent coronary DES implantation. Patients were followed up over 2 years. MACCE were defined as cardiac and cerebrovascular death, acute coronary syndrome, stroke, and HF hospitalization. Revascularization for asymptomatic patients were excluded. Pre-procedural serum levels of high-sensitivity CRP (hsCRP), VEGF, and two oxLDLs, serum-amyloid-A/LDL complex (SAA-LDL) and α1-antitrypsin/LDL complex (AT-LDL), were measured. During a median follow-up of 720 (IQR, 498-720) days, MACCE developed in a total of 39 patients (8.8%). Patients were divided into two groups based on the median of each biomarker. In Kaplan-Meier analyses, high-VEGF and high-SAA-LDL ( P =0.009, P =0.0498 by log-rank test, respectively), but not high-hsCRP or high-AT-LDL, were significantly associated with MACCE. Multivariate Cox proportional hazard analyses revealed that natural log-transformed VEGF levels (Ln-VEGF) (HR, 1.9 per 1 SD increase; 95% CI, 1.3 to 3.0; P =0.001), but not Ln-SAA-LDL (HR, 1.2; 95% CI, 0.89-1.5, P =0.3), Ln-hsCRP, or Ln-AT-LDL, was significantly associated with MACCE after adjustment for age, sex, and established risk factors. Finally, we performed stepwise multivariate Cox proportional hazard analysis including possible confounders, such as the number of lesions and type of DES, and these biomarkers. Notably, the independent predictors of MACCE were age (HR, 1.8 per 10 years; 95% CI, 1.2-2.7; P =0.004), Ln-VEGF (HR, 1.9; 95% CI, 1.2-3.1; P =0.005) and chronic kidney disease (HR, 2.5; 95% CI, 1.2-5.0; P =0.01). Conclusions: A high VEGF value may serve as a predictor of MACCE following coronary DES implantation.

In vitro оценка содержания лекарственных веществ и кинетики их выделения из коронарных стентов с различными типами полимерных покрытий

2019 ◽  
Vol 52 (12) ◽  
pp. 50-54
Author(s):  
Анна Игоревна Простякова ◽  
Дмитрий Игоревич Зыбин ◽  
Дмитрий Валерьевич Капустин
Keyword(s):  
Drug Eluting Stent ◽  
Drug Eluting

Изучение профиля выделения лекарственного средства in vitro — необходимый этап при оптимизации полимерно-лекарственной композиции в процессе разработки стентов, выделяющих лекарственное вещество (ЛВ). В статье представлены результаты ВЭЖХ-анализа содержания ЛВ и кинетики его выделения из различных типов полимерно-лекарственного покрытия выделяющих ЛВ коронарных стентов (drug eluting stent — DES): биодеградируемого покрытия с сиролимусом и стабильного покрытия с зотаролимусом. Содержание ЛВ оценивали для кримпированных стентов на системе доставки, а также после раскрытия. Продемонстрирована связь морфологии лекарственного покрытия с кинетикой выделения ЛВ и показано, что крупные морфологические дефекты покрытия приводят к отклонению параметров выделения ЛВ.

Recent In Vitro and In Silico Advances in the Understanding of Intranasal Drug Delivery

2020 ◽  
Vol 26 ◽  
Author(s):  
John Chen ◽  
Andrew Martin ◽  
Warren H. Finlay
Keyword(s):  
Drug Delivery ◽  
In Silico ◽  
Local Drug Delivery ◽  
In Vivo Studies ◽  
Intranasal Drug Delivery ◽  
Nasal Sprays ◽  
In Silico Studies ◽  
Drug Delivery Devices

Background: Many drugs are delivered intranasally for local or systemic effect, typically in the form of droplets or aerosols. Because of the high cost of in vivo studies, drug developers and researchers often turn to in vitro or in silico testing when first evaluating the behavior and properties of intranasal drug delivery devices and formulations. Recent advances in manufacturing and computer technologies have allowed for increasingly realistic and sophisticated in vitro and in silico reconstructions of the human nasal airways. Objective: To perform a summary of advances in understanding of intranasal drug delivery based on recent in vitro and in silico studies. Conclusion: The turbinates are a common target for local drug delivery applications, and while nasal sprays are able to reach this region, there is currently no broad consensus across the in vitro and in silico literature concerning optimal parameters for device design, formulation properties and patient technique which would maximize turbinate deposition. Nebulizers are able to more easily target the turbinates, but come with the disadvantage of significant lung deposition. Targeting of the olfactory region of the nasal cavity has been explored for potential treatment of central nervous system conditions. Conventional intranasal devices, such as nasal sprays and nebulizers, deliver very little dose to the olfactory region. Recent progress in our understanding of intranasal delivery will be useful in the development of the next generation of intranasal drug delivery devices.

scholarly journals Lipid Raft Association Stabilizes VEGF Receptor 2 in Endothelial Cells

2021 ◽  
Vol 22 (2) ◽  
pp. 798
Author(s):  
Ibukunoluwapo O. Zabroski ◽  
Matthew A. Nugent
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Lipid Rafts ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Potential Mechanism ◽  
Lysosomal Degradation ◽  
Extracellular Signal ◽  
The Stability ◽  
Endothelial Growth Factor

The binding of vascular endothelial growth factor A (VEGF) to VEGF receptor-2 (VEGFR-2) stimulates angiogenic signaling. Lipid rafts are cholesterol-dense regions of the plasma membrane that serve as an organizational platform for biomolecules. Although VEGFR2 has been shown to colocalize with lipid rafts to regulate its activation, the effect of lipid rafts on non-activated VEGFR2 has not been explored. Here, we characterized the involvement of lipid rafts in modulating the stability of non-activated VEGFR2 in endothelial cells using raft disrupting agents: methyl-β-cyclodextrin, sphingomyelinase and simvastatin. Disrupting lipid rafts selectively decreased the levels of non-activated VEGFR2 as a result of increased lysosomal degradation. The decreased expression of VEGFR2 translated to reduced VEGF-activation of the extracellular signal-regulated protein kinases (ERK). Overall, our results indicate that lipid rafts stabilize VEGFR2 and its associated signal transduction activities required for angiogenesis. Thus, modulation of lipid rafts may provide a means to regulate the sensitivity of endothelial cells to VEGF stimulation. Indeed, the ability of simvastatin to down regulate VEGFR2 and inhibit VEGF activity suggest a potential mechanism underlying the observation that this drug improves outcomes in the treatment of certain cancers.

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