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Background: The high lifetime risk of vascular disease is one of the important issues that plague patients with diabetes mellitus. Systemic oral vildagliptin administration favors endothelial recovery and inhibits smooth muscle cell (SMC) proliferation. However, the localized release of vildagliptin in the diabetic vessel damage has seldom been investigated., Research Design and Methods: In this work, nanofiber-eluting stents that loaded with vildagliptin, a dipeptidyl peptidase-4 enzyme (DPP-4) inhibitor, was fabricated to treat diabetic vascular disease. To prepare nanofibers, the poly (D,L)-lactide-co-glycolide (PLGA) and vildagliptin were mixed using hexafluoroisopropanol and electrospinning process. In vitro and in vivo release rates of the vildagliptin were characterized using high-performance liquid chromatography., Results: Effective vildagliptin concentrations were delivered for more than 28 days from the nanofibrous membranes coating on the surface of the stents in vitro and in vivo. The vildagliptin-eluting PLGA membranes greatly accelerated the recovery of diabetic endothelia and reduced SMC hyperplasia. The type I collagen content of the diabetic vascular intimal area that was treated by vildagliptin-eluting stents was lower than that of the non-vildagliptin-eluting group., Conclusion: The experimental results revealed that stenting with vildagliptin-eluting PLGA membranes could potentially promote healing for diabetic arterial diseases., Competing Interests: The authors report no conflicts of interest with respect to this work., (© 2019 Lee et al.)

Objective: The current treatment of atherosclerotic coronary heart disease with limus-eluting stents can lead to incomplete endothelialization and substantial impairment of arterial healing relative to treatment with bare-metal stents. The sustained and local delivery of ticagrelor, a reversibly binding P2Y12 receptor inhibitor, using hybrid biodegradable nanofibers/stents, was developed to reduce neointimal formation and endothelial dysfunction., Methods: In this investigation, a solution of ticagrelor, poly(D,L)-lactide-co-glycolide, and hexafluoro isopropanol was electrospun to fabricate ticagrelor-eluting nanofibrous drug-eluting stents. The in vitro and in vivo ticagrelor concentrations were measured using a high-performance liquid chromatography assay. The effectiveness of ticagrelor-eluting stents was examined relative to that of sirolimus-eluting stents., Results: Adequate ticagrelor levels were detected for four weeks in vitro. Less HES5-positive labeling was found near the ticagrelor-eluting stented vessels (0.33±0.12) than close to the sirolimus-eluting stented vessels (0.57±0.15) ( p <0.05). Four weeks after deployment, the ticagrelor-eluting stent also exhibited an up-regulated local expression of SOD1 in the stenting area ( p <0.001). The ticagrelor-eluting stent substantially preserved endothelial function and re-endothelialization, minimized inflammatory responses, and inhibited neointimal hyperplasia., Conclusion: Ticagrelor-eluting stents may provide an alternative route for treating patients at a high risk of bleeding to preserve endothelial recovery and to reduce smooth muscle proliferation., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

A novel bifurcation stent coated with bioabsorbable nanofibers that deliver the extended and controlled release of rosuvastatin and paclitaxel was developed. Bioabsorbable bifurcation stents, consisting of a double-slit tubular main body and two spiral branches, were manufactured. Bi-layered poly (lactic-co-glycolic acid) nanofibers that contained rosuvastatin and paclitaxel were used for treating the stents. Various properties of the fabricated stents, including compression strengths, collapse pressure, water contact angle and flow properties within a circulation model, were quantified. In vitro nanofibrous elution chromatography assays from the drug-loading bifurcation stents were carried out for the release patterns of pharmaceuticals. The effectiveness of eluted rosuvastatin and paclitaxel in inhibiting the adhesion of platelets as well as the proliferation of smooth muscle cells (SMCs) were studied, respectively. The experimental results suggest that bioabsorbable nanofibrous bifurcation stents released high concentrations of rosuvastatin and paclitaxel for 27 and 70 days, respectively. The eluted drugs of rosuvastatin and paclitaxel effectively reduced adherent platelets and the proliferation of SMCs. The developed bioabsorbable nanofibrous bifurcation stents herein may provide a promising means of treating cardiovascular bifurcation lesions., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: The drug-eluting stent is a standard approach for the treatment of coronary artery disease. Propylthiouracil (PTU), an antithyroid drug, has been proven to suppress neointimal formation after balloon injury., Materials and Methods: This study used a biodegradable polymer coating with PTU to test its effects on platelet function, re-endothelialization, and neointimal formation after vascular injury. Electrospinning was used to fabricate hybrid stents and generate PTU-loaded nanofibers., Results: PTU-eluting stents maintained a stable release of PTU for 3 weeks. The PTU-coated stent markedly decreased the neointimal formation induced by vascular injury in the descending aorta of rabbits. Moreover, the PTU coating reduced platelet adhesion on the surface of the biodegradable membrane, which was reflected by the decreased expression of adhesion molecule in PTU-treated endothelial cells. The PTU coating enhanced re-endothelialization in injured aortas. In vitro, PTU exerted less suppressive effect on the proliferation and migration of endothelial cells than on those of vascular smooth muscle cells. Furthermore, treatment of endothelial cells with PTU induced phosphorylation (Ser1177) of endothelial nitric oxide synthase as well as its association with heat shock protein 90, supporting the protective role of PTU in endothelial function. The level of thyroid-stimulating hormone remained unchanged during the experimental period., Conclusion: This study indicates that PTU can be released locally and steadily in injured aortas, with some local effects but without systemic effects. Furthermore, PTU-coated stents may have beneficial effects on neointimal formation, endothelial cell, and platelet functions., Competing Interests: Disclosure US patent (6,939,863) using PTU for the prevention of atherosclerosis and restenosis has been licensed by Wei-Jan Chen. The authors report no other conflicts of interest in this work.

"Cable-tie" type biodegradable stents with drug-eluting nanofiber were developed to treat rabbit denuded arteries in this study. Biodegradable stents were fabricated using poly-L-lactide film following being cut and rolled into a cable-tie type stent. Additionally, drug-eluting biodegradable nanofiber tubes were electrospun from a solution containing poly (lactic-co-glycolic acid), rapamycin, and hexafluoroisopropanol, and then mounted onto the stents. The fabricated rapamycin-eluting cable-tie stents exhibited excellent mechanical properties on evaluation of compression test and collapse pressure, and less than 8% weight loss following being immersed in phosphate-buffered saline for 16 weeks. Furthermore, the biodegradable stents delivered high rapamycin concentrations for over 4 weeks and achieved substantial reductions in intimal hyperplasia associated with elevated heme oxygenase-1 and calponin level on the denuded rabbit arteries during 6 months of follow-up. The drug-eluting cable-tie type stents developed in this study might have high potential impacts for the local drug delivery to treat various vascular diseases.

This study describes novel biodegradable, drug-eluting nanofiber-loaded vascular prosthetic grafts that provide local and sustained delivery of vancomycin to surrounding tissues. Biodegradable nanofibers were prepared by first dissolving poly(D,L)-lactide-co-glycolide and vancomycin in 1,1,1,3,3,3-hexafluoro-2-propanol. The solution was then electrospun into nanofibers onto the surface of vascular prostheses. The in vitro release rates of the pharmaceutical from the nanofiber-loaded prostheses was characterized using an elution method and a high-performance liquid chromatography assay. Experimental results indicated that the drug-eluting prosthetic grafts released high concentrations of vancomycin in vitro (well above the minimum inhibitory concentration) for more than 30 days. In addition, the in vivo release behavior of the drug-eluting grafts implanted in the subcutaneous pocket of rabbits was also documented. The drug-eluting grafts developed in this work have potential applications in assisting the treatment of vascular prosthesis infection and resisting reinfection when an infected graft is to be exchanged.

Introduction: This work reports on the development of a biodegradable dual-drug-eluting stent with sequential-like and sustainable drug-release of anti-platelet acetylsalicylic acid and anti-smooth muscle cell (SMC) proliferative paclitaxel., Methods: To fabricate the biodegradable stents, poly-L-lactide strips are first cut from a solvent-casted film. They are rolled onto the surface of a metal pin to form spiral stents. The stents are then consecutively covered by acetylsalicylic acid and paclitaxel-loaded polylactide-polyglycolide nanofibers via electrospinning., Results: Biodegradable stents exhibit mechanical properties that are superior to those of metallic stents. Biodegradable stents sequentially release high concentrations of acetylsalicylic acid and paclitaxel for more than 30 and 60 days, respectively. In vitro, the eluted drugs promote endothelial cell numbers on days 3 and 7, and reduce the proliferation of SMCs in weeks 2, 4, and 8. The stents markedly inhibit the adhesion of platelets on days 3, 7, and 14 relative to a non-drug-eluting stent. In vivo, the implanted stent is intact, and no stent thrombosis is observed in the stent-implanted vessels without the administration of daily oral acetylsalicylic acid. Promotion of endothelial recovery and inhibition of neointimal hyperplasia are also observed on the stented vessels., Conclusion: The work demonstrates the efficiency and safety of the biodegradable dual-drug-eluting stents with sequential and sustainable drug release to diseased arteries.

Incomplete endothelialization and neointimal hyperplasia of injured arteries can cause acute and late stent thromboses. This work develops hybrid stent/biodegradable nanofibers for the local and sustained delivery of rosuvastatin to denuded artery walls. Biodegradable nanofibers were firstly prepared by dissolving poly(D,L)-lactide-co-glycolide and rosuvastatin in 1,1,1,3,3,3-hexafluoro-2-propanol. The solution was then electrospun into nanofibrous tubes, which were mounted onto commercially available bare-metal stents. The in vitro release rates of the pharmaceuticals from the nanofibers were determined using an elution method and a high-performance liquid chromatography assay. The experimental results thus obtained suggest that the biodegradable nanofibers released high concentrations of rosuvastatin for four weeks. The effectiveness of the local delivery of rosuvastatin in reducing platelets was studied. The tissue inflammatory reaction caused by the hybrid stents that were used to treat diseased arteries was also documented. The proposed hybrid stent/biodegradable rosuvastatin-loaded nanofibers contributed substantially to the local and sustainable delivery of a high concentration of drugs to promote re-endothelialization, improve endothelial function, reduce inflammatory reaction, and inhibit neointimal formation of the injured artery. The results of this work provide insight into how patients with a high risk of stent restenosis should be treated for accelerating re-endothelialization and inhibiting neointimal hyperplasia., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Self-expandable metallic stents (SEMSs) are effective in the palliation of malignant airway obstruction. Tumor ingrowth, however, frequently occurs because of a shortage of effective local therapy. Additionally, SEMSs are frequently associated with problems of fracture, migration, and difficult removals. Our goal was to develop a novel bioabsorbable stent with cisplatin elution to circumvent such problems., Methods: Biodegradable stents made of polycaprolactone were fabricated by a laboratory-made, microinjection molding machine. In vitro mechanical strength of the stents was compared with the strength of Ultraflex SEMSs. Polylactide-polyglycolide copolymer and cisplatin were coated onto the surfaces of the stents. Elution method and high-performance liquid chromatography (HPLC) analysis were used to examine the in vitro cisplatin release characteristics. In vivo, the stents were surgically implanted into the cervical trachea of 15 New Zealand white rabbits. Bronchoscopic examination was performed weekly (1 to approximately 5 weeks) before killing. Cisplatin concentrations in trachea, lung, and blood were analyzed by HPLC. Histologic examination was also performed., Results: The biodegradable stent exhibited mechanical strength comparable to the strength of Ultraflex SEMSs and provided a steady release of cisplatin for >4 weeks in vitro. The in vivo study showed sustained cisplatin levels in rabbit trachea for >5 weeks with a minimum drug level in blood. Histologic examination showed an intact ciliated epithelium and marked leukocyte infiltration in the submucosa of the stented area., Conclusions: Our study demonstrated that the biodegradable stents provided physical properties comparable to the properties of SEMSs and a sustained release of cisplatin for >5 weeks, which showed great potential in the treatment of malignant airway obstruction.

In this report, a balloon-expandable, biodegradable, drug-eluting bifurcation stent (DEBS) that provides a sustainable release of anti-proliferative sirolimus was developed. Biodegradable bifurcation stents, made of polycaprolactone, were first manufactured by injection molding and hot spot welding techniques. Various properties of the fabricated stents, including compression strengths, collapse pressures, and flow pattern in a circulation test, were characterized. The experimental results showed that biodegradable bifurcation stents exhibited comparable mechanical properties with those of metallic stents and superior flow behavior to that of metallic bifurcation stents deployed via the T And small Protrusion approach. Polylactide-polyglycolide (PLGA) copolymer and sirolimus were then dissolved in acetonitrile and coated onto the surface of the stents by a spray coating device. An elution method and a high performance liquid chromatography analysis were utilized to examine the in vitro release characteristics of sirolimus. Biodegradable bifurcation stents released high concentrations of sirolimus for more than 6 weeks, and the total period of drug release could be prolonged by increasing the drug loading of the PLGA/sirolimus coating layers. In addition, the eluted drug could effectively inhibit the proliferation of smooth muscle cells. The developed DEBS in this study may provide a promising strategy for the treatment of cardiovascular bifurcation lesions.

The purpose of this report was to develop novel balloon-expandable self-lock drug-eluting poly(ε-caprolactone) stents. To fabricate the biodegradable stents, polycaprolactone (PCL) components were first fabricated by a lab-scale micro-injection molded machine. They were then assembled and hot-spot welded into mesh-like stents of 3 and 5 mm in diameters. A special geometry of the components was designed to self-lock the assembled stents and to resist the external pressure of the blood vessels after being expanded by balloons. Characterization of the biodegradable PCL stents was carried out. PCL stents exhibited comparable mechanical property to that of metallic stents. No significant collapse pressure reduction and weight loss of the stents were observed after being submerged in PBS for 12 weeks. In addition, the developed stent was coated with paclitaxel by a spray coating technique and the release characteristic of the drug was determined by an in vitro elution method. The high-performance liquid chromatography analysis showed that the biodegradable stents could release a high concentration of paclitaxel for more than 60 days. By adopting the novel techniques, we will be able to fabricate biodegradable drug-eluting PCL stents of different sizes for various cardiovascular applications.

Various effective methods are available for perioperative pain control in osteosynthesis surgery, but they are seldom applied intraoperatively. The aim of this study was to evaluate a biodegradable poly([d,l]-lactide-co-glycolide) (PLGA)/lidocaine nanofibrous membrane for perioperative pain control in rib fracture surgery. Scanning electron microscopy showed high porosity of the membrane, and an ex vivo high-performance liquid chromatography study revealed an excellent release profile for both burst and controlled release of lidocaine within 30 days. Additionally, the PLGA/lidocaine nanofibrous membrane was applied in an experimental rabbit rib osteotomy model. Implantation of the membrane around the osteotomized rib during osteosynthesis surgery resulted in a significant increase in weight gain, food and water consumption, and daily activity compared to the study group without the membrane. In addition, all osteotomized ribs were united. Thus, application of the PLGA/lidocaine nanofibrous membrane may be effective for sustained relief of pain in oeteosynthesis surgery. [ABSTRACT FROM AUTHOR]

The purpose of this report was to develop solvent-free biodegradable drug-eluting implants that provide sustained release of metronidazole and doxycycline. The drug-eluting implants were prepared using the compression molding technique. To fabricate the implants, polylactide-polyglycolide copolymers were premixed with metronidazole or doxycycline. The mixture was then compression molded and sintered to form implants of various sizes and geometries. An elution method and an HPLC assay were used to characterize the in vitro release rates of the antibiotics over a 28-day period. A bacterial inhibition test was also carried out to determine the bioactivity of released antibiotics. The concentrations of both metronidazole and doxycycline were much greater than the minimum inhibitory concentration of Escherichia coli for up to 3 and 4 weeks, respectively, and the bioactivities of the antibiotics remained high after the fabrication process. Furthermore, the initial burst could be minimized and the release rate could be reduced by increasing the size of the implants and by adopting low drug to polymer ratios. By using this compression molding technique and appropriate processing parameters, we will be able to fabricate biodegradable implants of various types of antibacterial drugs for long-term local deliveries. Eventually, biodegradable drug-eluting implants may be used to treat various periodontal diseases. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2012 [ABSTRACT FROM AUTHOR]

[Display omitted] • We designed an amalgamated scaffold. • We fabricated a polycaprolactone tubular stent. • We electrospun collagen/drugs-embedded nanofibrous mats. • The scaffold promoted the treatment of tendon rupture. Despite the progress made in modern medical technology, the therapy of ruptured tendons continues to be a challenging task. We designed an amalgamated scaffold consisting of an additively manufactured polycaprolactone (PCL) tubular stent and electrospun collagen/drug-embedded poly-D-L-lactide-glycolide (PLGA) nanofibrous mats for the treatment of Achilles tendon rupture. The in vitro drug elution characteristics of pharmaceuticals from electrospun nanofibers was estimated. The in vivo efficacies of PCL stent/biomolecules-biomolecule-eluting nanofibers for the therapy of treatment of tendon rupture were also evaluated on in a rabbit model with histological examinations. The experimental results showed that the PCL stents with diamond pores exhibited the best mechanical properties. Drug-loaded PLGA nanofibers provided sustained discharges of vancomycin and ceftazidime for 40 days and lidocaine for over 10 days in vitro. The in vivo outcomes suggested that the repaired tendon strengths in the no-stent group and stent-only group (without drugs) showed poorer strength than the control (normal tendons with no surgery). Furthermore, the stent/drug group exhibited a higher recovery rate than the stent-only group. The integration of the additively manufactured PCL tubular stent and electrospun drug-eluting PLGA nanofibrous membranes can effectively enhance tendon treatment in a rabbit model. [ABSTRACT FROM AUTHOR]

The purpose of this study is to develop biodegradable drug-eluting pellets to provide a sustainable delivery of cisplatin intrapleurally. Poly( d , l )-lactide- co -glycolide (PLGA) (LA:GA = 50:50) copolymer and cisplatin were mixed, compressed, and sintered to construct biodegradable pellets and placed in phosphate-buffered saline to test the characteristics of in vitro release. In vivo, equal amounts of cisplatin (10 mg/kg) were introduced into rabbit pleural cavities either by free form (Gr1) or pellets form (Gr2). Cisplatin concentrations in the collected pleural effusion and blood were measured and compared by repeated measurement ANOVA. In vitro, approximately 5% of the cisplatin was released in the first day while the rest was gradually released in the following 50 days. In vivo, the cisplatin level in the pleural fluid was equally high during the first 2 days but dropped quickly in Gr1 while remaining high in Gr2 for 18 days, the difference was statistically significant ( P < 0.001) In contrast, the plasma cisplatin level was 10 times significantly higher in Gr1 than in Gr2 ( P < 0.001), which resulted in two early deaths of rabbits. Thus we concluded that our biodegradable pellets could achieve high and steady cisplatin release in the pleural cavity. This novel drug delivery system may have the potential to serve as an adjuvant treatment for malignant pleural lesion. [ABSTRACT FROM AUTHOR]