Safety evaluation of self‐expanding metallic biliary stents eluting gemcitabine in a porcine model

Chung, Moon Jae; Kim, Hyunki; Kim, Kyung Sik; Park, Sangsoo; Chung, Jae Bock; Park, Seung Woo

doi:10.1111/j.1440-1746.2011.06866.x

Cited by 44 publications

(27 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Polyurethane films incorporated with paclitaxel (PTX) have been used in suppressing malignant tumor growth around biliary stents as well as benign tissue hyperplasia caused by placement of esophageal and urethral stents [57,[60][61][62][63]. When gemcitabine was incorporated in a polyurethane film, in vitro release behavior and in vivo toxicity of the gemcitabine were studied in an animal model [9,37,38]. IN1233, an activin receptor-like kinase-5 inhibitor, was also incorporated in a stent covered with a polyurethane film and delivered to rabbit esophagus for evaluation of its effect on suppression of neointimal hyperplasia after esophageal stenting [45].…”

Section: Drug Eluting Non-vascular Stentmentioning

confidence: 99%

“…Although there has been a clinical trial of PTX-eluting biliary stent for suppressing malignant tumor around the stent, the previous study failed to show efficacy of PTX-eluting stent, compared to the ordinary stent without PTX [70]. The safety of gemcitabine-releasing stent has been studied in a canine model, but its clinical application is yet to be tried [9]. Further study on how to control the drug release rate of these drugs is warranted for clinical success of the stent-based delivery of these anti-proliferative drugs.…”

Section: Drug Eluting Non-vascular Stentmentioning

confidence: 99%

“…A stent is a cylindrical medical device usually made of metallic or polymeric wires that could be placed in the blood vessel [1][2][3][4][5][6] and the non-vascular lumen including gastrointestinal, upper respiratory, and urinary tract to alleviate the symptoms caused by the stenosis [7][8][9][10][11][12][13][14]. Since stenting has been demonstrated to be one of the most successful treatment modality in the interventional medicine, the application range of stenting has been expanding fast.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Local Delivery of Antiproliferative Agents via Stents

Kwon

Park

2014

Polymers

Self Cite

View full text Add to dashboard Cite

Abstract:A stent is a medical device for serving as an internal scaffold to maintain or increase the lumen of a body conduit. Stent placement has become a primary treatment option in coronary artery disease for more than the last two decades. The stenting is also currently used for relieving the symptoms of narrowed lumen of nonvascular organs, such as esophagus, trachea and bronchi, small and large intestines, biliary, and urinary tract. Local delivery of active pharmaceutical agents via the stents can not only enhance healing of certain diseases, but it can also help decrease the potential risk of the stenting procedure to the surrounding tissue. In this review, we focus on reviewing a variety of drug-impregnated stents and local drug delivery systems using the stents.

show abstract

Section: Drug Eluting Non-vascular Stentmentioning

confidence: 99%

Section: Drug Eluting Non-vascular Stentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Local Delivery of Antiproliferative Agents via Stents

Kwon

Park

2014

Polymers

Self Cite

View full text Add to dashboard Cite

show abstract

“…Concentrated proteins (50 mg) were mixed with nonreducing sample buffer (0.5 M Tris-HCl pH 6.8, 4% SDS, 20% glycerol, 0.1% bromophenol blue) at a 1:1 ratio and electrophoresed on 8% SDS-polyacrylamide gels (SDS-PAGE) containing 2 mg/mL gelatin (Bio Basic, Markham, ON, Canada) under nonreducing conditions. After electrophoresis, the gel was washed three times for 30 …”

Section: Gelatin Zymographymentioning

confidence: 99%

Preclinical evaluation of sorafenib-eluting stent for suppression of human cholangiocarcinoma cells

Kim

Jeong²,

Chung³

et al. 2013

IJN

View full text Add to dashboard Cite

Background: Cholangiocarcinoma is a malignant tumor arising from the epithelium of the bile ducts. In this study, we prepared sorafenib-loaded biliary stents for potential application as drug-delivery systems for localized treatment of extrahepatic cholangiocarcinoma. Methods: A sorafenib-coated metal stent was prepared using an electrospray system with the aid of poly(ε-caprolactone) (PCL), and then its anticancer activity was investigated using human cholangiocellular carcinoma (HuCC)-T1 cells in vitro and a mouse tumor xenograft model in vivo. Anticancer activity of sorafenib against HuCC-T1 cells was evaluated by the proliferation test, matrix metalloproteinase (MMP) activity, cancer cell invasion, and angiogenesis assay in vitro and in vivo. Results: The drug-release study showed that the increased drug content on the PCL film induced a faster drug-release rate. The growth of cancer cells on the sorafenib-loaded PCL film surfaces decreased in a dose-dependent manner. MMP-2 expression of HuCC-T1 cells gradually decreased according to sorafenib concentration. Furthermore, cancer cell invasion and tube formation of human umbilical vein endothelial cells significantly decreased at sorafenib concentrations higher than 10 mM. In the mouse tumor xenograft model with HuCC-T1 cells, sorafenib-eluting PCL films significantly inhibited the growth of tumor mass and induced apoptosis of tumor cells. Various molecular signals, such as B-cell lymphoma (Bcl)-2, Bcl-2-associated death promoter, Bcl-x, caspase-3, cleaved caspase-3, Fas, signal transducer and activator of transcription 5, extracellular signal-regulated kinases, MMP-9 and pan-janus kinase/stress-activated protein kinase 1, indicated that apoptosis, inhibition of growth and invasion was cleared on sorafenibeluting PCL films. Conclusion: These sorafenib-loaded PCL films are effective in inhibiting angiogenesis, proliferation and invasion of cancer cells. We suggest that sorafenib-loaded PCL film is a promising candidate for the local treatment of cholangiocarcinoma.

show abstract

“…Until recently, the challenge in developing a gemcitabine-eluting stent was the hydrophilic nature of this drug, since most of the drug is eluted initially, with little left for sustained elution during the stent lifetime. The authors have recently published their pilot experience with gemcitabine-eluting SEMS in a porcine model [16]. To date, however, human experience with gemcitabine stents is lacking.…”

mentioning

confidence: 99%

Drug-Eluting Stents in Malignant Biliary Obstruction: Where Do We Stand?

Shah

2012

Dig Dis Sci

View full text Add to dashboard Cite

In patients with malignant biliary obstruction, endoscopic placement of biliary stents offers similar technical success rates but a lower risk of complications and a trend towards decreased mortality when compared to surgical bypass and percutaneous drainage [1,2]. As a result, over the last three decades, endoscopic retrograde cholangiography (ERC)-guided stent placement has become the preferred approach to palliate malignant biliary obstruction.Until the 1990s, only plastic stents were available. Plastic stents may occlude within 3-6 months, often requiring repeated ERC procedures in order to exchange the stents. The introduction of a stainless-steel uncovered metal stent (Wallstent, Boston Scientific) heralded a major advance in extending the duration of stent patency. Although self-expandable metallic stents (SEMS) are more expensive than plastic stents, they are cost-effective when compared to plastic stents for patients expected to live longer than 3 months due to the need for fewer subsequent ERC procedures [1,[3][4][5][6]. Nonetheless, SEMS do eventually occlude in 19-40 % of patients [3][4][5]. The duration of SEMS patency has remained largely unchanged in spite of modifications in stent composition and the addition of a plastic coating [7][8][9]. Thus, a clear need exists for technologic improvements that minimize stent occlusion.The major mechanisms of SEMS occlusion are tumor ingrowth, tumor overgrowth, and epithelial hyperplasia. These mechanisms provide the rationale for developing a stent that is coated with or locally elutes a chemotherapeutic agent in order to improve stent patency. In vitro and animal studies suggest that a paclitaxel-coated stent may be safe and potentially efficacious when used for malignant biliary obstruction. Kalinoswki et al. [10] demonstrated that incubation with paclitaxel inhibited proliferation of human gallbladder cells, human fibroblasts, and pancreatic cells in a dose-dependent fashion. In a porcine model, SEMS coated with a paclitaxel-incorporated membrane were not associated with transmural necrosis or perforation [11]. Paclitaxel-eluting stents also appear to be safe in a canine model [12].Limited data exist regarding outcomes of paclitaxeleluting stents for malignant biliary obstruction in humans. In a pilot study of 21 humans with malignant biliary obstruction, SEMS coated with a paclitaxel-incorporated membrane remained patent for a mean of 429 days (cumulative patency rate at 3, 6, and 12 months of 100, 71, and 36 %, respectively) [13]. The pilot study suggests a paclitaxel-coated SEMS may provide longer patency rates than the 10-12 months provided by standard uncovered or covered SEMS and informed the author's decision to proceed with a larger prospective study [1].The current study by the same investigators is a prospective comparison of standard covered SEMS to SEMS covered by a paclitaxel-incorporated membrane [14]. Stents were 5-8 cm in length and 10 mm in diameter in both groups. The authors initially planned the study as a randomized controlled trial...

show abstract

Safety evaluation of self‐expanding metallic biliary stents eluting gemcitabine in a porcine model

Abstract: Our newly developed GEM eluting stents can be used safely in normal bile ducts. Our results indicated that 10% GEM produced mild histologic changes in the stented segment and adjacent tissue; this concentration may be appropriate for clinical application.

Cited by 44 publications

References 32 publications

Local Delivery of Antiproliferative Agents via Stents

Local Delivery of Antiproliferative Agents via Stents

Preclinical evaluation of sorafenib-eluting stent for suppression of human cholangiocarcinoma cells

Drug-Eluting Stents in Malignant Biliary Obstruction: Where Do We Stand?

Contact Info

Product

Resources

About