Arsenic trioxide-eluting electrospun nanofiber-covered self-expandable metallic stent reduces granulation tissue hyperplasia in rabbit trachea

Abstract

Stent-related granulation tissue hyperplasia is a major complication that limits the application of stents in airways. In this study, an arsenic trioxide-eluting electrospun nanofiber-covered self-expandable metallic stent (ATO-NFCS) was developed. Poly-L-lactide-caprolactone (PLCL) was selected as the drug-carrying polymer. Stents with two different ATO contents (0.4% ATO/PLCL and 1.2% ATO/PLCL) were fabricated. The in vitro release in simulated airway fluid suggested that the total ATO release time was 1 d. The growth of human embryonic pulmonary fibroblasts (CCC-HPF-1), normal human bronchial epithelial cells and airway smooth muscle cells was inhibited by ATO. When embedded in paravertebral muscle, the nanofiber membrane showed good short-term and long-term biological effects. In an animal study, placement of the ATO-NFCS in the trachea through a delivery system under fluoroscopy was feasible. The changes in liver and kidney function 1 and 7 d after ATO-NFCS placement were within the normal range. On pathological examination, the heart, liver, spleen, lungs and kidneys were normal. The effectiveness of the ATO-NFCS in reducing granulation tissue hyperplasia and collagen deposition was demonstrated in the rabbit airway (n = 18) at 4 weeks. The present study preliminarily investigated the efficacy of the ATO-NFCS in reducing granulation tissue formation in the trachea of rabbits. The results suggest that the ATO-NFCS is safe in vivo, easy to place, and effective for the suppression of granulation tissue formation.

State of the Science in Tracheal Stents: A Scoping Review

“…Hybrid stents are often referred to as a “covered” or “coated” stents. In our review, 19 studies employed hybrid stents as outlined in Tables I–III 4,20,27,36–51 . This diverse group of stents utilized a stainless steel or nitinol framework coated with polyurethane (n = 7), 20,27,40–42,44,48 silicone (n = 3), 39,49,50 expanded polytetrafluoroethylene (n = 1), 49 polyester (n = 1), 49 polypropylene (n = 1), 49 unspecified material (n = 4), 4,38,43,45 and drug‐eluting polymers (n = 3) 46,47,51 .…”

“…Nineteen studies utilized different polymers as stent materials 15,46,47,51–66 . Only one of these represented a human clinical study where polydioxanone (PDS) stents were used in four patients 64 .…”

“…Five studies employed drug‐eluting stents, all exploring a different target drug (Table III). Mitomycin C, paclitaxel, rapamycin, doxycycline, and arsenic trioxide were evaluated in preclinical animal models 46,47,51,53,65 . All studies were preclinical, and included three leporine studies, one murine study, and one canine study.…”

“…Drug‐eluting stent studies seem to hold the most promise, though many of those still need to clear regulatory hurdles for implementation in human studies. Two drug‐eluting studies investigated an electrospun polymer as a means to facilitate drug elution/delivery that was applied to a commonly‐used expandable metal stent “backbone” to facilitate endoscopic insertion 46,47 . Another promising new technology that deserves attention is the use of a custom 3D printed polymer intraluminal stent 58 .…”

Synergistic effects of silver nanoparticles and cisplatin in combating inflammation and hyperplasia of airway stents

“…The electrospinning parameters and drug content of the fiber films were as recommended in previous reports [ [23] , [24] , [25] , [26] ]. In brief, 1.25 g of PCL was first dissolved in 10 mL of hexafluoroisopropanol (HFIP) to prepare the PCL solution.…”