Sirolimus-Eluting Electrospun-Produced Matrices as Coatings for Vascular Stents: Dependence of Drug Release on Matrix Structure and Composition of the External Environment

Although a number of drug-eluting coatings for vascular stents (VSs) have been developed and are in commercial use, more efficient stent coatings and drug delivery systems are needed. Sirolimus (SRL) is a clinically important drug with antiproliferative and immunosuppressive activities that is widely used for coating stents. Here, we characterized SRL-enriched matrices, intended for coating vascular stents, that were produced by electrospinning (ES) on a drum collector from a solution of polycaprolactone (PCL) and human serum albumin (HSA), 1,1,1,3,3,3-hexafluoroisopropanol (HFIP), dimethyl sulfoxide (DMSO), and SRL. The release of tritium-labeled SRL (3H-SRL) from matrices in phosphate-buffered saline (PBS) or human blood plasma (BP) was studied. The introduction of DMSO in the ES blend decreased SRL release. The use of BP significantly accelerated SRL release through binding with serum biomolecules. The exchange of PBS or BP after every time point also increased SRL release. The maximum SRL release in BP was observed at 3 days. The matrices produced from the ES solution with DMSO and HSA released no more than 80% SRL after 27 days in BP, even under medium exchange conditions. Therefore, PCL-based matrices containing HSA, SRL, and DMSO can be used for coating VSs with prolonged SRL delivery.

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Influence of Elongation of Paclitaxel-Eluting Electrospun-Produced Stent Coating on Paclitaxel Release and Transport Through the Arterial Wall after Stenting

Polymers ◽

10.3390/polym13071165 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1165

Author(s):

Zhanna K. Nazarkina ◽

Boris P. Chelobanov ◽

Konstantin A. Kuznetsov ◽

Alexey V. Shutov ◽

Irina V. Romanova ◽

...

Keyword(s):

Drug Release ◽

Arterial Wall ◽

Release Kinetics ◽

Artery Wall ◽

Vascular Stents ◽

Drug Eluting ◽

Fiber Breaks ◽

Stent Diameter ◽

Stent Coating

It was previously shown that polycaprolactone (PCL)-based electrospun-produced paclitaxel (PTX)-enriched matrices exhibit long-term drug release kinetics and can be used as coatings for drug-eluting stents (DES). The installation of vascular stents involves a twofold increase in stent diameter and, therefore, an elongation of the matrices covering the stents, as well as the arterial wall in a stented area. We studied the influence of matrix elongation on its structure and PTX release using three different electrospun-produced matrices. The data obtained demonstrate that matrix elongation during stent installation does not lead to fiber breaks and does not interfere with the kinetics of PTX release. To study PTX diffusion through the expanded artery wall, stents coated with 5%PCL/10%HSA/3%DMSO/PTX and containing tritium-labeled PTX were installed into the freshly obtained iliac artery of a rabbit. The PTX passing through the artery wall was quantified using a scintillator β-counter. The artery retained the PTX and decreased its release from the coating. The retention of PTX by the arterial wall was more efficient when incubated in blood plasma in comparison with PBS. The retention/accumulation of PTX by the arterial wall provides a prolonged drug release and allows for the reduction in the dose of the drugs in electrospun-produced stent coatings.

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Progress on precise regulation of vascular intimal repair by surface coating of vascular stent

Current Drug Delivery ◽

10.2174/1567201818666210212100633 ◽

2021 ◽

Vol 18 ◽

Author(s):

Shihui Liu ◽

Junchao Zhi ◽

Shijie Li ◽

Zhuoyue Song ◽

Tao Gong ◽

...

Keyword(s):

Clinical Performance ◽

Biological Response ◽

Research Direction ◽

Vascular Stent ◽

Functional Layer ◽

Vascular Stents ◽

Drug Eluting ◽

Genetic Level ◽

Disease Related Gene

: In the past few decades, drug-eluting stents have made significant contributions to the treatment of coronary heart disease. However, due to the delayed healing of endothelial injuries caused by antiproliferative drugs and insufficient biocompatibility of vascular stent materials, late in-stent thrombosis and restenosis remain major challenges. Surface modification of cardiovascular materials to construct biological functional layer that can regulate the behavior of blood and vascular cells is an effective way to improve the clinical performance of vascular stents. This paper reviewed the common methods of surface bio-functional modification of cardiovascular materials, and especially proposed that take the advantage of the new concept of precision medicine, as well as the precise and orderly regulation properties of cardiovascular disease-related gene fragments on vascular biological response behavior, the construction of gene-eluting stents which can in-situ regulate vascular intimal repair at the molecular and genetic level will become an important research direction in the future.

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Nanotechnology Applications in Biomedical Engineering

Handbook of Research on Diverse Applications of Nanotechnology in Biomedicine, Chemistry, and Engineering - Advances in Chemical and Materials Engineering ◽

10.4018/978-1-4666-6363-3.ch004 ◽

2015 ◽

pp. 50-63

Author(s):

Cajetan M. Akujuobi

Keyword(s):

Dental Implants ◽

21St Century ◽

Biomedical Engineering ◽

Well Being ◽

Orthopedic Implants ◽

Vascular Stents ◽

Safety Aspects ◽

Drug Eluting ◽

And Mathematics ◽

The Impact

The 21st century has seen a massive explosion in the applications of nanotechnology. These applications cover all areas of Science, Technology, Engineering, and Mathematics (STEM). The advantage of nanotechnology comes from the fact that it has revolutionized the miniaturizations of many products that are useful to the well-being of society. A typical nanotechnology application example in biomedical engineering is its usage as drug eluting interfaces for implantable devices, such as vascular stents, orthopedic implants, and dental implants. The purpose of this chapter is to discuss the various applications of nanotechnology to biomedical engineering. Some of the future nanotechnology applications in biomedical engineering include healthcare/medical, consumer medical goods, environmental, and electronics. The impact of nanotechnology applications to biomedical engineering is in many ways enabling humans to survive different ailments that otherwise could have been very difficult to manage. The safety aspects in the applications of nanotechnology to biomedical engineering are also examined.

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Nanotechnology Applications in Biomedical Engineering

Oncology ◽

10.4018/978-1-5225-0549-5.ch012 ◽

2017 ◽

pp. 352-365 ◽

Cited By ~ 1

Author(s):

Cajetan M. Akujuobi

Keyword(s):

Dental Implants ◽

21St Century ◽

Biomedical Engineering ◽

Well Being ◽

Orthopedic Implants ◽

Vascular Stents ◽

Safety Aspects ◽

Drug Eluting ◽

And Mathematics ◽

The Impact

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SCANNING ION MICROBEAM ANALYSIS OF DIFFUSION IN IN-MOUTH DRUG RELEASE POLYMERS

International Journal of PIXE ◽

10.1142/s0129083505000477 ◽

2005 ◽

Vol 15 (03n04) ◽

pp. 161-167 ◽

Cited By ~ 2

Author(s):

G. MASSINGHAM ◽

R. ARSLANOGLU ◽

F. E. GAUNTLETT ◽

M. S. RIHAWY ◽

R. W. SMITH ◽

...

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Nuclear Reaction ◽

Drug Delivery Systems ◽

Saline Solution ◽

Pure Water ◽

X Ray ◽

Preliminary Results ◽

Water Infusion ◽

Phosphate Buffered Saline

With the aim of characterizing polymer-based drug delivery systems a combination of Scanning MeV 3 He microbeam Nuclear Reaction, Backscattering and Particle Induced X-ray Emission (PIXE) techniques has been developed. This, together with gravimetric and UV techniques has been applied to characterize both water infusion and drug effusion for three in-mouth polymer–drug systems. Preliminary results are presented from the exposure of polymers, containing drug at a level of 9% by weight of the dry polymer, to both pure water and a phosphate buffered saline solution at 37°C.

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Expression of macrophage CD14 receptor in the course of experimental inflammatory responses induced by lipopolysaccharide and muramyl dipeptide

Veterinární Medicína ◽

10.17221/1991-vetmed ◽

2008 ◽

Vol 53 (No. 7) ◽

pp. 347-357 ◽

Cited By ~ 4

Author(s):

Z. Sladek ◽

D. Rysanek

Keyword(s):

Inflammatory Response ◽

Inflammatory Responses ◽

Early Stage ◽

Muramyl Dipeptide ◽

Cell Suspensions ◽

The Other ◽

Total Count ◽

The Difference ◽

Phosphate Buffered Saline ◽

Time Point

The aim of this study was to determine whether expression of CD14 on macrophages is regulated differently during initiation and resolution of the inflammatory response caused by CD14-dependent (lipopolysaccharide) and CD14-independent (muramyldipeptide) bacterial signals. In cell suspensions from the site of inflammation we observed two types of macrophages: non-vacuolized (NMAC) and vacuolized (VMAC) cells. NMAC (monocyte-like cells) were dominant during the early stage of the inflammatory response, whilst VMAC contained phagocytosed apoptotic neutrophils in various stages of digestion. These latter cells were dominant during resolution (particularly at the last time point of 168 h). Intramammary instillation of muramyldipeptide (MDP) and lipopolysaccharide (LPS) resulted in a significant increase in the total count of CD14+ NMAC after 24 h (muramyldipeptide P < 0.01 and lipopolysaccharide P < 0.05) compared to phosphate buffered saline (PBS). During resolution of the inflammatory response, a gradual decrease in the total count of CD14+ NMAC was observed. The difference compared with PBS was significant at 48 h and 72 h after instillation of both bacterial agents (muramyldipeptide: P < 0.05; lipopolysaccharide: P < 0.05). A lower total count of CD14+ VMAC was observed as an effect of MDP and LPS at 24 h after induction (P < 0.05), when compared to PBS. During resolution, the total count of CD14+ VMAC increased. Differences (P < 0.01) were observed at 72 h and 168 h after LPS compared to PBS. We therefore assume that the expression of CD14 on macrophages is not regulated differently during the inflammatory responses caused by CD14-dependent and CD14-independent bacterial signals. On the other hand, the stage of the inflammatory response to MDP and LPS played an important role in the regulation of CD14 expression on macrophages.

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Vascular Stents Coated with Electrospun Drug-Eluting Material: Functioning in Rabbit Iliac Artery

Polymers ◽

10.3390/polym12081741 ◽

2020 ◽

Vol 12 (8) ◽

pp. 1741

Author(s):

Konstantin A. Kuznetsov ◽

Ivan S. Murashov ◽

Vera S. Chernonosova ◽

Boris P. Chelobanov ◽

Alena O. Stepanova ◽

...

Keyword(s):

Blood Flow ◽

Iliac Artery ◽

Balloon Catheter ◽

Bare Metal Stents ◽

Blood Flow Rate ◽

Metal Stents ◽

Bare Metal ◽

Vascular Stents ◽

Drug Eluting

A stenting procedure aimed at blood flow restoration in stenosed arteries significantly improves the efficiency of vascular surgery. However, the current challenge is to prevent neointimal growth, which reduces the vessel lumen, in the stented segments in the long run. We tested in vivo drug-eluting coating applied by electrospinning to metal vascular stents to inhibit the overgrowth of neointimal cells via both the drug release and mechanical support of the vascular wall. The blend of polycaprolactone with human serum albumin and paclitaxel was used for stent coating by electrospinning. The drug-eluting stents (DESs) were placed using a balloon catheter to the rabbit common iliac artery for 1, 3, and 6 months. The blood flow rate was ultrasonically determined in vivo. After explantation, the stented arterial segment was visually and histologically examined. Any undesirable biological responses (rejection or hemodynamically significant stenosis) were unobservable in the experimental groups. DESs were less traumatic and induced weaker neointimal growth; over six months, the blood flow increased by 37% versus bare-metal stents, where it increased by at least double the rate. Thus, electrospun-coated DESs demonstrate considerable advantages over the bare-metal variants.

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Sirolimus-Loaded Polyurethane Graft for Hemodialysis Access in Sheep

Vascular ◽

10.2310/6670.2008.00032 ◽

2008 ◽

Vol 16 (5) ◽

pp. 269-274 ◽

Cited By ~ 7

Author(s):

Earl Schuman ◽

Jayaraman Babu

Keyword(s):

Intimal Hyperplasia ◽

Measured Parameter ◽

Hemodialysis Access ◽

Ultrasound Evaluation ◽

Coated Materials ◽

Elution Curves ◽

Table Analysis ◽

Drug Eluting ◽

Arteriovenous Grafts ◽

Time Point

Intimal hyperplasia is the most common final pathway for hemoaccess occlusion in dialysis patients. Drug eluting stents have been shown to decrease intimal hyperplasia in coronary arteries and possibly in peripheral arteries. We evaluated the use of a sirolimus loaded polyurethane graft as prophylaxis in hemodialysis access. Grafts were loaded with sirolimus and elution curves were determined for the polyurethane material. The arteriovenous grafts were then placed in the neck of 20 sheep. A non-loaded graft was placed in the contralateral neck. Patency rates, ultrasound evaluation, angiography and histomorphometry were determined for each graft. At 30, 60 and 90 days the drug loaded graft had improved patency rates compared to the control, with a 25% improvement noted at 3 months. Life table analysis showed the drug loaded graft consistently better patency than the control (p = .136). The control graft had greater neointimal stenosis (14.5% vs 9.17%) over the course of the study (p = .157). Although none of these findings was statistically significant in this pilot study, the sirolimus coated graft out-performed the control in every measured parameter at each time point evaluated. Further work to asses the validity of drug coated materials to prevent intimal hyperplasia in hemodialysis access is warranted.

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mRECIST and EASL responses at early time point by contrast-enhanced dynamic MRI predict survival in patients with unresectable hepatocellular carcinoma (HCC) treated by doxorubicin drug-eluting beads transarterial chemoembolization (DEB TACE)

Annals of Oncology ◽

10.1093/annonc/mds605 ◽

2013 ◽

Vol 24 (4) ◽

pp. 965-973 ◽

Cited By ~ 70

Author(s):

H.J. Prajapati ◽

J.R. Spivey ◽

S.I. Hanish ◽

B.F. El-Rayes ◽

J.S. Kauh ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Transarterial Chemoembolization ◽

Early Time ◽

Dynamic Mri ◽

Early Time Point ◽

Unresectable Hepatocellular Carcinoma ◽

Contrast Enhanced ◽

Drug Eluting Beads ◽

Drug Eluting ◽

Time Point

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Alpha-Ketoglutarate: A Potential Inner Mitochondrial and Cytosolic Protector against Peroxynitrite and Peroxynitrite-Induced Nitration?

Antioxidants ◽

10.3390/antiox10091501 ◽

2021 ◽

Vol 10 (9) ◽

pp. 1501

Author(s):

Joachim Greilberger ◽

Michaela Greilberger ◽

Reinhold Wintersteiger ◽

Klaus Zangger ◽

Ralf Herwig

Keyword(s):

Bovine Serum Albumin ◽

Final Concentration ◽

Nmr Studies ◽

Tyrosine Residues ◽

Negative Linear Correlation ◽

Elisa Technique ◽

Cancer Inflammation ◽

Phosphate Buffered Saline ◽

Oxidative Species ◽

Time Point

The generation of peroxynitrite (ONOO−) is associated with several diseases, including atherosclerosis, hypertension, neurodegeneration, cancer, inflammation, and sepsis. Alpha-ketoglutarate (αKG) is a known potential highly antioxidative agent for radical oxidative species such as peroxides. The question arises as to whether αKG is also a potential scavenger of ONOO− and a potential protector against ONOO−-mediated nitration of proteins. NMR studies of 1 mM αKG in 100 mM phosphate-buffered saline at pH 7.4 and pH 6.0 were carried out in the presence or absence of a final concentration of 2 mM ONOO−. An ONOO−–luminol-induced chemiluminescence reaction was used to measure the scavenging function of several concentrations of αKG; quantification of αKG was performed via spectrophotometric enzymatic assay of αKG in the absence or presence of 0, 1, or 2 mM ONOO−. The nitration of tyrosine residues on proteins was measured on ONOO−-treated bovine serum albumin (BSA) in the presence or absence of 0–24 mM αKG by an ELISA technique using a specific anti-IgG against nitro-tyrosine. The addition of ONOO− to αKG led to the formation of succinic acid and nitrite at pH 7.0, but not at pH 6.0, as αKG was stable against ONOO−. The absorbance of enzymatically estimated αKG at the time point of 30 min was significantly lower in favour of ONOO− (1 mM: 0.21 ± 0.03, 2 mM: 0.12 ± 0.05 vs. 0 mM: 0.32 ± 0.02; p < 0.001). The luminol technique showed an inverse logarithmic correlation of the ONOO− and αKG concentrations (y = −2 × 105 ln(x) + 1 × 106; r2 = 0.99). The usage of 4 mM αKG showed a significant reduction by nearly half in the chemiluminescence signal (284,456 ± 29,293 cps, p < 0.001) compared to the control (474,401 ± 18,259); for 20 and 200 mM αKG, there were further reductions to 163,546 ± 26,196 cps (p < 0.001) and 12,658 ± 1928 cps (p < 0.001). Nitrated tyrosine residues were estimated using the ELISA technique. A negative linear correlation was obtained by estimating nitrated tyrosine residues in the presence of αKG (r2 = 0.94): a reduction by half of nitrated tyrosine was estimated using 12 mM αKG compared to the control (326.1 ± 39.6 nmol vs. 844.5 ± 128.4 nmol; p < 0.001).

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