Drug-eluting non-vascular stents for localised drug targeting in obstructive gastrointestinal cancers

Arafat, Mohammad; Fouladian, Paris; Blencowe, Anton; Albrecht, Hugo; Song, Yunmei; Garg, Sanjay

doi:10.1016/j.jconrel.2019.07.001

Cited by 25 publications

(31 citation statements)

References 98 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, chemotherapeutics consistently released from DESs over a sustained period of time are more likely to result in optimal diffusion and uptake by the surrounding cancer cells over several cell division cycles and may lead to better control of GI tumor cell replication and subsequent cancer spread. 1 , 65 Hence, GI DESs could potentially inhibit the growth of cancer cells around the stent more efficiently than conventional systemic administration of chemotherapeutics and non-DESs. 6 , 9 , 10 , 13 , 18–20 , 23 , 66–68 …”

Section: Resultsmentioning

confidence: 99%

“…Conventional gastrointestinal (GI) stents have a proven track record of clinical safety and effectiveness in the localized management of stenoses and/or obstructions. 1 Nevertheless, in-stent restenosis (ISR) is a common problem due to benign hyperplastic or malignant tissue growth within the stented region. 1–3 ISR frequently results in a significant reduction in the effective duration of the stenting treatment, thus necessitating placement of a second stent or emergency surgical intervention.…”

Section: Introductionmentioning

confidence: 99%

“… 1 Nevertheless, in-stent restenosis (ISR) is a common problem due to benign hyperplastic or malignant tissue growth within the stented region. 1–3 ISR frequently results in a significant reduction in the effective duration of the stenting treatment, thus necessitating placement of a second stent or emergency surgical intervention. 1–4 While the introduction of vascular drug-eluting stents (DESs) has drastically reduced the incidence of ISR among coronary artery disease (CAD) patients, 2 , 5 , 6 the translation of GI DESs towards the clinic holds promise for the treatment of ISR and simultaneous reduction of tumor burden for GI cancers.…”

Section: Introductionmentioning

confidence: 99%

“… 26 To date, various biostable and biodegradable polymers have been investigated in combination with different self-expandable metal stents (SEMSs) for the fabrication of DES platforms. 1 , 27 , 28 However, biostable polymers are preferable for GI DES, as biodegradable polymer coatings could result in early stent blockage due to malignant tumor growth, stricture recurrence, or stent migration. 1 , 27 While biostable polyurethanes (PUs), polysiloxanes, and poly(ethylene-co-vinyl acetate) (PEVA) have been commonly used for DES applications, 7 , 27 , 29 PUs offer excellent biocompatibility and mechanical properties, and can readily be combined with drugs.…”

Section: Introductionmentioning

confidence: 99%

“… 1 , 27 , 28 However, biostable polymers are preferable for GI DES, as biodegradable polymer coatings could result in early stent blockage due to malignant tumor growth, stricture recurrence, or stent migration. 1 , 27 While biostable polyurethanes (PUs), polysiloxanes, and poly(ethylene-co-vinyl acetate) (PEVA) have been commonly used for DES applications, 7 , 27 , 29 PUs offer excellent biocompatibility and mechanical properties, and can readily be combined with drugs. 1 , 27 Nevertheless, the high aqueous solubility of 5FU (13.26 mg/mL) 30 can potentially result in burst release profiles, and therefore, it is advantages to incorporate a drug-free protective layer to slow the diffusion and release kinetics of 5FU from coated stents.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Pharmaceutical Development of 5-Fluorouracil-Eluting Stents for the Potential Treatment of Gastrointestinal Cancers and Related Obstructions

Arafat¹,

Song²,

Brewer³

et al. 2021

DDDT

Self Cite

View full text Add to dashboard Cite

Background Drug-eluting gastrointestinal (GI) stents are emerging as promising platforms for the treatment of GI cancers and provide the combined advantages of mechanical support to prevent lumen occlusion and as a reservoir for localized drug delivery to tumors. Therefore, in this work we present a detailed quality assurance study of 5-fluorouracil (5FU) drug-eluting stents (DESs) as potential candidates for the treatment of obstructive GI cancers. Methods The 5FU DESs were fabricated via a simple two-step sequential dip-coating process of commercial GI self-expanding nitinol stents with a 5FU-loaded polyurethane basecoat and a drug-free protective poly(ethylene-co-vinyl acetate) topcoat. The drug loading, content uniformity and drug stability were determined using a validated high-performance liquid chromatography (HPLC) method, which is also recommended in the United States Pharmacopeia. In vitro drug release studies were performed in phosphate buffered saline to determine the drug releasing properties of the two 5FU-loaded stents. Gas chromatography (GC) and HPLC were employed to determine total residual tetrahydrofuran and N,N -dimethylformamide in the stents remaining from the manufacturing process. Sterilization of the stents was performed using gamma radiation and stability testing was carried out for 3 months. Results The drug loading analysis revealed excellent uniformity in the distribution of 5FU between and within individual stents. Determination of drug stability in the biorelevant release media confirmed that 5FU remains stable over 100 d. In vitro drug release studies from the stents revealed sustained release of 5FU across two different time scales (161 and 30 d), and mathematical modeling of drug release profiles revealed a diffusion-controlled mechanism for the sustained 5FU release. GC and HPLC analysis revealed that the daily residual solvent leached from the stents was below the United States (US) Food and Drug Administration (FDA) guidelines, and therefore, unlikely to cause localized/systemic toxicities. Sterilization of the stents with gamma radiation and accelerated stability tests over a period of 3 months revealed no significant effect on the stability or in vitro release of 5FU. Conclusion Our results demonstrate that the 5FU DESs meet relevant quality standards and display favourable drug release characteristics for the potential treatment of GI cancers and related obstructions.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Pharmaceutical Development of 5-Fluorouracil-Eluting Stents for the Potential Treatment of Gastrointestinal Cancers and Related Obstructions

Arafat¹,

Song²,

Brewer³

et al. 2021

DDDT

Self Cite

View full text Add to dashboard Cite

show abstract

Utilizing 4D Printing to Design Smart Gastroretentive, Esophageal, and Intravesical Drug Delivery Systems

Mahmoud

Schulz‐Siegmund

2023

Adv Healthcare Materials

View full text Add to dashboard Cite

The breakthrough of 3D printing in biomedical research has paved the way for the next evolutionary step referred to as four dimensional (4D) printing. This new concept utilizes the time as the fourth dimension in addition to the x, y, and z axes with the idea to change the configuration of a printed construct with time usually in response to an external stimulus. This can be attained through the incorporation of smart materials or through a preset smart design. The 4D printed constructs may be designed to exhibit expandability, flexibility, self-folding, self-repair or deformability. This review focuses on 4D printed devices for gastroretentive, esophageal, and intravesical delivery. The currently unmet needs and challenges for these application sites are tried to be defined and reported on published solution concepts involving 4D printing. In addition, other promising application sites that may similarly benefit from 4D printing approaches such as tracheal and intrauterine drug delivery are proposed.

show abstract

Biosynthetic Plastics as Tunable Elastic and Visible Stent with Shape‐Memory to Treat Biliary Stricture

et al. 2023

View full text Add to dashboard Cite

Common biliary tract is ≈4 mm in diameter to deliver bile from liver to small intestine to help digestion. The abnormal narrowing leads to severe symptoms such as pain and nausea. Stents are an effective treatment. Compared with non‐degradable stents which require repeated removal, biodegradable stents have the advantage of reducing secondary injury related to endoscopic operation and patient burden. However, current biodegradable materials may cause tissue hyperplasia and the treatment method does not target etiology of stricture. So recurrence rates after biodegradable stent implantation are still high. Here, a biodegradable helical stent fabricated from biosynthetic P(3HB‐co‐4HB) is reported. Tunable properties can be acquired through altering culture substrates. Stent shows shape memory in various solvents. The stent has an optimized design with helical structure and outer track. The self‐expanding of helical structure and double drainage realized by outer track greatly improve drainage of bile. Importantly, stent‐loading triamcinolone acetonide can inhibit proliferation of fibroblasts and reduce incidence of restricture. Therapeutic effect is also demonstrated in minipigs with biliary stricture. The results of minipig experiments show that biliary duct in treatment group is unobstructed and tissue hyperplasia is effectively inhibited.

show abstract

Drug-eluting non-vascular stents for localised drug targeting in obstructive gastrointestinal cancers

Cited by 25 publications

References 98 publications

Pharmaceutical Development of 5-Fluorouracil-Eluting Stents for the Potential Treatment of Gastrointestinal Cancers and Related Obstructions

Pharmaceutical Development of 5-Fluorouracil-Eluting Stents for the Potential Treatment of Gastrointestinal Cancers and Related Obstructions

Utilizing 4D Printing to Design Smart Gastroretentive, Esophageal, and Intravesical Drug Delivery Systems

Biosynthetic Plastics as Tunable Elastic and Visible Stent with Shape‐Memory to Treat Biliary Stricture

Contact Info

Product

Resources

About