sirolimus and glycolic-acid

Drug-eluting stents (DESs) implantation is an effective method to tackle in-stent restenosis (ISR), which has been considered as an efficient treatment for coronary atherosclerosis. Although fruitful results have been achieved in treating coronary artery diseases (CAD), concern has arisen regarding the long-term safety and efficacy of DESs, primarily due to adverse events such as delayed re-endothelialization, persistent inflammatory response, and late stent thrombosis (LST). Taking inspiration from the immunomodulatory functions of camouflage strategies, this study designed a bio-inspired nanoparticle-coated stent. Briefly, the platelet membrane-coated poly (lactic-co-glycolic acid)/Rapamycin nanoparticles (PNP) were sprayed onto stents, forming a homogenous nanoparticle coating. The bilayer of poly (lactic-co-glycolic acid) (PLGA) and platelet membrane works synergistically to promote the sustained-release effect of rapamycin. In vitro studies revealed that the PNP-coated surfaces promoted the competitive adhesion of endothelia cells while inhibiting smooth muscle cells. Subsequent in vivo studies demonstrated that these surfaces expedite re-endothelialization and elicit immunomodulatory effects by regulating the cGMP-PKG and NF-kappa B signaling pathways, influencing the biosynthesis cofactors and immune system signaling. The study successfully deviced a novel and biomimetic drug-eluting stent system, unraveling its detailed functions and molecular mechanism of action for enhanced vascular healing.

Topics: Drug-Eluting Stents; Nanoparticles; NF-kappa B; Signal Transduction; Sirolimus; Stents

Ureteral stricture caused by holmium: YAG laser lithotripsy is one of the most challenging issues for urologists. Currently, evidence for rapamycin application in reducing ureterostenosis is not sufficient. This study aimed to assess the inhibition of ureteral stricture of rapamycin-eluting stents in vitro and in vivo. A bilayered drug-eluting ureteral stent consisted of drug blending with poly (lactic-co-glycolic acid) (PU/drug stent), which was over-layered by polycaprolactone (PCL) by ultrasonic atomizing spraying. Stent morphology was observed by scanning electron microscope. A kidney-ureter-bladder model was established to simulate the stents-releasing condition, and high-performance liquid chromatography was used to measure the drug release rate. The inhibitory proliferation was detected by CCK-8. The bladder of rats was injured through electro tome, and stents were implanted for 7, 14, and 28 days. The effects of drug-eluting stents was investigated by hematoxylin-eosin staining, immunofluorescence staining, real-time quantitative polymerase chain reaction and western blot. The bilayered stents could block the burst loss of the drug and maintained a sustained delivery period because of the 5.3 μm thickness of the PCL layer. The relative growth rates of cells plotted inhibitory effect on the proliferation of human urethral scar fibroblast cells. For in vivo results of 28 days, the bilayered stent maintained structural integrity and induced less deposition of crystals, thinner and less lamina propria connective tissues were formed, and α-SMA and TGF-β1 were downregulated. Bilayered rapamycin-eluting stent is significantly effective in alleviating fibrosis in in vitro and in vivo models. STATEMENT OF SIGNIFICANCE: The occurrence of ureteral stricture resulting from holmium: YAG laser lithotripsy presents a significant challenge for urologists. Traditional double J stents have not been proven to offer a shorter indwelling time or improved inhibition of tissue blocking. While drug-eluting stents containing rapamycin, paclitaxel, and other substances have been extensively used in treating artery stenosis, there is insufficient evidence supporting their application in reducing ureterostenosis. Consequently, a biodegradable polymer ureteric scaffold incorporating rapamycin was fabricated in this study, employing ultrasonic atomization spraying technology to optimize the bilayers composed of 75/25 poly (lactic-co-glycolic acid) (PLGA) and polycaprolactone (

Topics: Animals; Constriction, Pathologic; Drug-Eluting Stents; Holmium; Humans; Lithotripsy, Laser; Rats; Sirolimus; Stents