Nondestructive Extraction and Identification of Microplastics from Freshwater Sport Fish Stomachs.

Microplastics were extracted from freshwater sport fish stomachs containing substantial biomass and identified using optical microscopy, scanning electron microscopy plus energy-dispersive X-ray spectroscopy (SEM/EDS), and Fourier transform infrared (FTIR) micro-spectroscopy with automated spectral mapping. An extraction method is presented that uses a negatively pressurized sieve stack and purified water to preserve plastic surface characteristics and any adsorbed persistent organic pollutants (POPs). This nondestructive extraction method for large predators' stomachs enables multiple trophic-level studies from one fish sampling event and provides other dietary and behavioral data. FTIR-identified microplastics 50-1500 µm, including polyethylene (two with plastic additive POPs), styrene acrylonitrile, polystyrene, and nylon and polyethylene terephthalate fibers 10-50 µm wide. SEM/EDS revealed characteristic surface weathering on the plastic surfaces. The nylon fibers appear to be from human fishing activities, suggesting options for management. Some particles visually identified as potential plastics were revealed by micro-spectroscopy to be mineralized, natural polyamide proteins, or nonplastic shell pieces. A low-cost, reflective sample preparation method with stable particle mounting was developed to enable automated mapping, improved FTIR throughput, and lower detection size limit. This study yielded 37 intact prey items set aside for future analyses.

Preparation and characterization of a novel polyethyleneimine cation-modified persimmon tannin bioadsorbent for anionic dye adsorption.

A novel and recyclable bioadsorbent (PTP) has been prepared by the cationization of persimmon tannin (PT) using polyethyleneimine (PEI) for application in the removal of the anionic dye methyl orange (MO) from aqueous solution. The physicochemical properties of the prepared PTP were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, Zeta potential measurements, Brunauer-Emmett-Teller and thermogravimetric analysis. Systematic batch adsorption experiments were carried out with pH, bioadsorbent dosage, initial MO concentration and contact time. Kinetic regression analysis indicated that the adsorption processes followed the pseudo-second order model. The equilibrium isotherm was in good fit with the Freundlich model with a maximum adsorption capacity of 225.74 mg/g. Thermodynamics data revealed that the adsorption of MO onto PTP was feasible, spontaneous and endothermic. A possible biosorption mechanism was presented where electrostatic interactions, hydrogen bonding, and π-π interactions dominated the adsorption of MO onto PTP. Moreover, the regeneration of the PTP was easily achieved and MO removal efficiency remained high (81.47%) after six cycles. The actual sewage treatment simulation was evaluated and the PTP had a good preference to adsorption MO. All these results indicated that PTP could be considered a high performance and promising candidate for the effective removal of anionic dyes from aqueous solutions.

Analysis of the effect of paclitaxel-eluting stents and paclitaxel-eluting balloon in the treatment of in-stent restenosis.

To compare and analyze the effect and the safety of the paclitaxel-eluting stents and paclitaxel-eluting balloon in the treatment for in-stent rest enosis. 120 cases, who had been undergone percutaneous coronary intervention (PCI) in the Department of Cardiology of Henan Provincial People's Hospital from January 2012 to January 2014 were selected. All the patients were randomly treated with paclitaxel-eluting balloon or paclitaxel-eluting stents. The former were divided into different groups that named group A and the later group B. All the selected patients signed the informed consent on interventional therapy and be given anti-platelet drugs before operating. At the same time, they had routine examination, like chest X-ray, ultrasound, biochemical detection, Myocardial injury markers. (1) The two groups had no significant difference in the general information (P>0.05); (2) The success rate in the two groups reached 100% and (3) All the patients were visited in the 9th, 12th and 24th month to see if any of them was dead. The reexamination results in the 9th month showed that both drug-eluting balloon and drug-eluting stents were safe and effective in treating coronary artery in-stent restenosis. In addition, drug-eluting balloon was more effective than drug-eluting stents to prevent from the in-stent restenosis.

Nitinol stents loaded with a high dose of antitumor 5-fluorouracil or paclitaxel: esophageal tissue responses in a porcine model.

BACKGROUND: A poor prognosis associated with esophageal cancer leads to surgical resection not suitable for most patients. Nitinol stents loaded with 50% 5-fluorouracil (5-FU) or paclitaxel (PTX), functioning both as a stent and local chemotherapy, could provide a new therapy modality for these patients. OBJECTIVE: To investigate esophageal tissue responses to nitinol stents loaded with 50% 5-FU or PTX implanted in the esophagus of healthy pigs. DESIGN: Twenty-three healthy Bama mini-pigs were randomly divided into 4 groups for stent implantation: group A (PTX stent, n = 13), group B (5-FU stent, n = 8), group C (blank film-covered stent, n = 1), and group D (bare stent, n = 1). Tissue responses were observed by endoscopy or pathologic analyses, and 5-FU or PTX concentrations were measured in the esophagus at the stent implantation site at different time points. SETTING: Animal laboratory. INTERVENTIONS: Endoscopic placement of esophagus stent. MAIN OUTCOME MEASUREMENTS: Endoscopic examination, histology, and drug concentration analysis. RESULTS: In general, the esophageal tissue responses varied according to different parts of 5-FU or PTX stent (middle part [drug-containing part] and bare ends [drug-free part]). Severe tissue responses at the bare ends of the stent included inflammation, ulceration, and granulation. However, the tissue responses were greatly reduced in the middle part of the stent. The drug concentrations in the esophagus that had contact with the 5-FU stent or PTX stent were very high, especially for the first period after implantation, which did not cause obvious tissue damage. LIMITATION: Some subjects had incomplete follow-up because of unexpected deaths and stent migration. CONCLUSION: The nitinol stents loaded with 50% 5-FU or PTX did not cause severe esophageal tissue responses, although there was a large concentration of the drug in these tissues.

A spherical adsorbent produced from a bagasse biochar chitosan assembly for selective adsorption of platinum-group metals from wastewater.

This study addresses the challenge of platinum-group metal scarcity by exploring the adsorption of these metals from industrial wastewater. An inexpensive adsorbent with selective platinum-group metal adsorption capacity, named chitosan/citric acid@diatomaceous earth-sugarcane bagasse (CTS/CA@DE-SBS), was newly synthesized. The material features a double coating of chitosan and diatomite on bagasse biochar, and it exhibits an excellent adsorption performance for platinum-group metals due to the synergistic effects of the biochar and chitosan-diatomaceous earth intercross-linked coatings. CTS/CA@DE-SBS achieved an 81 % adsorption efficiency and a static saturated adsorption capacity of 217 mg/g for Pt (IV) in water. Notably, the material exhibited selective adsorption properties for platinum-group metals dissolved in diverse aqueous solutions. The potential for the secondary recovery of platinum-group metals in complex aqueous bodies further underscores the significance of this adsorbent. In conclusion, this research introduces a promising solution for platinum-group metal shortages, offering a cost-effective and selective adsorbent with potential applications in the secondary recovery of these metals from industrial wastewater.

Photonic Hyperthermia Synergizes with Immune-Activators to Augment Tumor-Localized Immunotherapy.

Photothermal immunotherapy, the combination of photothermal hyperthermia and immunotherapy, is a noninvasive and desirable therapeutic strategy to address the deficiency of traditional photothermal ablation for tumor treatment. However, insufficient T-cell activation following photothermal treatment is a bottleneck to achieve satisfactory therapeutic effectiveness. In this work, a multifunctional nanoplatform is rationally designed and engineered on the basis of polypyrrole-based magnetic nanomedicine modified by T-cell activators of anti-CD3 and anti-CD28 monoclonal antibodies, which have achieved robust near infrared laser-triggered photothermal ablation and long-lasting T-cell activation, realizing diagnostic imaging-guided immunosuppressive tumor microenvironment regulation following photothermal hyperthermia by reinvigorating tumor-infiltrating lymphocytes. By virtue of high-efficient immunogenic cell death and dendritic cell maturation combined with T-cell activation, this nanosystem markedly restrains primary and abscopal tumors as well as metastatic tumors with negligible side effects in vivo, exerting the specific function for suppressing tumor recurrence and metastasis by establishing a long-term memory immune response.

Concurrent remission of lymphoma and Sjögren's disease following anti-CD19 chimeric antigen receptor-T cell therapy for diffuse large B-cell lymphoma: a case report.

Anti-CD19 chimeric antigen receptor (CAR)-T cells not only target CD19-positive malignant lymphoma cells but also normal B cells. The utility of CAR-T cell therapy has been reported in rheumatoid arthritis and systemic lupus erythematosus; however, its use in Sjögren's disease (SjD) remains unknown. In this study, we describe the case of a 76-year-old woman with active SjD for 10 years who was diagnosed with diffuse large B-cell lymphoma. After receiving anti-CD19 CAR-T cell therapy, she achieved complete remission (CR) on day 28. Since the onset of her 10-year history with SjD, she was negative for antinuclear antibodies and anti-Ro-52 for the first time on day 90 after CAR-T cell therapy. Six months after CAR-T cell therapy, the CR status was maintained, serum cytokine levels returned to their normal levels, and dry mouth symptoms improved. The EULAR Sjögren's Syndrome Disease Activity Index score decreased from 5 to 2, indicating a partial remission of SjD activity compared with that before CAR-T cell treatment. In the early stage of treatment, she presented with grade 2 cytokine release syndrome and grade 1 neurotoxicity, which were completely controlled after an active intervention. This case highlights the potential application of CAR-T cells in treating autoimmune diseases, such as SjD.

Structural optimization and in vivo evaluation of a colorectal stent with anti-migration and anti-tumor properties.

Clinically, colorectal stents can only palliatively relieve obstruction caused by colorectal cancer (CRC), with a high incidence of stent migration and tumor-related re-obstruction. To overcome these shortcomings, we developed a colorectal stent composed of a structure-optimized nitinol braided stent and a tubular film including an inner layer of poly (ethylene-co-vinyl acetate) (EVA) and a segmental outer layer of EVA with paclitaxel (PTX). The braiding pattern, segment number, and end shape of the stent were optimized based on the mechanical properties, ex vivo and in vivo anti-migration performance, and tissue response of the stent. The optimized nitinol stent had a structure of one middle segment in a hook-pattern and two end segments in a cross-pattern with two studs on each end in a staggered arrangement. Structure-optimized colorectal stents were prepared and evaluated in vivo. PTX released from the stent was mostly distributed in the rabbit rectum in contact with it. The biosafety of the colorectal stent was evaluated using blood tests, biochemical analysis, anatomical observation, and pathological analysis. The anti-tumor effect of the stent was also evaluated by endoscopy, anatomical observation, and pathological and immunohistochemical analyses in rabbits with orthotopic CRC. The results demonstrate that the optimized colorectal stents have effective anti-migration ability and anti-tumor effects with good biosafety. STATEMENT OF SIGNIFICANCE: In order to overcome the most common disadvantages of migration and re-obstruction of colorectal stents clinically, a colorectal stent composed of a structure-optimized nitinol stent and a tubular film including an inner layer of EVA and a segmental outer layer of EVA with PTX was put forward in this study. The optimized nitinol stent had a structure of one middle segment in hook-pattern and two end segments in cross-pattern with two studs on each end in staggered arrangement. The resulting colorectal stent has been proved with good anti-migration ability, anti-tumor effects, and biosafety in vivo, which provides a safe and effective potential treatment modality for patients with colorectal cancer.

Evaluation of two polymeric blends (EVA/PLA and EVA/PEG) as coating film materials for paclitaxel-eluting stent application.

The ethylene vinyl acetate copolymer (EVA)/Poly (lactic acid) (PLA) blend and EVA/Poly (ethylene glycol) (PEG) blend were applied as the drug carrier materials for a bi-layer drug-loaded stent coating film, which consisted of a paclitaxel (PTX)-loaded layer and a drug-free EVA layer. The changes of weight and appearance of the drug-free polymeric blend films with increasing time were examined by X-ray diffraction analysis (XRD), gel permeation chromatography (GPC) tests and scanning electronic microscopy (SEM), and the results showed the degradation of PLA and the leaching of PEG from the films. The effects of PLA, PEG and drug contents on in vitro drug release were investigated, and the results demonstrated that the addition of PLA promoted the drug release while the addition of PEG almost did not. Franz cells diffusion test results indicated that the bi-layer structure successfully endowed the stent coating with the release of drug in a unidirectional fashion. The release profiles of films incorporated PTX and the mechanical performance of the film could be customized by readily adjusting the contents of the blend components. Therefore, the polymeric blends could be useful drug carrier materials for drug-loaded stent coating capable of releasing drug in a highly tunable manner.

Self-Assembled Micelles of Amphiphilic PEGylated Drugs for Cancer Treatment.

Generally, poor solubility and imprecise delivery of chemotherapeutic drugs can compromise their efficacies for clinical cancer treatment. In order to address such concerns, poor water-soluble drugs are conjugated with poly(ethylene glycol) (PEG) to obtain PEGylated drugs, which have improved water solubility and can also self-assemble in an aqueous solution to form micelles (PEGylated drug micelles). The surface PEG layer enhances the micelles' colloidal stability and reduces the interaction with physiological surroundings. Meanwhile, PEGylated drug micelles are tumor- targeting via the enhanced permeation and retention (EPR) effect to improve antitumor efficacy in comparison with free drugs. PEGylated drug micelles employ drugs as parts of the carrier medium, which increases the micelles' drug loading capacity relatively. The development of stimuli- responsive PEGylated drug micelles facilitates the drug release to be smart and controllable. Moreover, the PEGylated drug micelles show great potentials in overcoming the challenges of cancer therapy, such as multidrug resistance (MDR), angiogenesis, immunosuppression, and so on. In this review, we highlight the research progresses of PEGylated drug micelles, including the structures and properties, smart stimuli-responsive PEGylated drug micelles, and the challenges that have been overcome by PEGylated drug micelles.

A new method for microplastic extraction from fish guts assisted by chemical dissolution.

A new protocol for the extraction of microplastic is proposed and demonstrated which combines dissection, ultrasonication, and filtration with chemical dissolution in order to estimate microplastic contamination in fish or other samples with significant biomass. This protocol enables initial characterization of the sample through dissection followed by chemical dissolution to isolate polymer debris while minimizing analytical uncertainties and maintaining microplastic particle integrity. The extraction method begins with dissection and inspection of the stomach contents, followed by pulsed ultrasonic extraction to remove the majority of biomass and surface contaminants. Subsequent chemical dissolution of the extracted contents using KOH and HCl removes any remaining biomass and inorganic interferences. Incorporating chemical dissolution post-extraction minimizes the overall biomass subjected to dissolution, thereby enabling faster processing and subsequently a cleaner sample compared to methods involving digestion of the entire organism. Furthermore, the chemical dissolution step enables direct filter analysis for microplastics, thereby minimizing the potential loss of microplastic particles associated with manual particle transfer. Hence, the microplastic extraction method presented here is suitable for the extraction and identification of small (>20 µm) and potentially brittle microplastic.

Tailor-made ternary nanopolyplexes of thiolated trimethylated chitosan with pDNA and folate conjugated cis-aconitic amide-polyethylenimine for efficient gene delivery.

To overcome the different extra-/intracellular barriers in gene delivery, tumor-targeted and pH/redox-responsive ternary polyplexes with charge-conversional properties were prepared through a modular self-assembly strategy. Firstly, the thiolated trimethylated chitosan (TMC-SH) was synthesized to crosslink and condense pDNA through electrostatic interaction and disulfide formation, which obtained the TMC-SS/pDNA binary polyplexes with redox-responsive gene release. To further endow the binary polyplexes with tumor targeting and endo/lysosomal pH-triggered charge-reversal properties, a folate conjugated cis-aconitic amide-polyethylenimine (FA-PEI-AcO) was synthesized to shield the positive TMC-SS/pDNA, generating the FA-PEI-AcO/TMC-SS/pDNA ternary polyplexes with a size of ~190 nm and negative surface-charges. The ζ-potential of the polyplexes was stable at physiological pH and increased rapidly from -14 mV to + 20 mV at pH 5.5 (endo/lysosomal pH) due to the breakages of acid-liable amide bonds and the subsequent de-shielding of FA-PEI-AcO layers, which might benefit the endo/lysosomal escape of the polyplexes. Afterward, the polyplexes could redox-responsively release gene at higher intracellular concentrations of glutathione. By taking advantage of such multi-responses, significantly enhanced transfection efficiency was achieved in vitro in Hela cells for the ternary polyplexes. These results suggested that the newly developed polyplexes had potential application for gene delivery.

Molecular identification of polymers and anthropogenic particles extracted from oceanic water and fish stomach - A Raman micro-spectroscopy study.

Pacific Ocean trawl samples, stomach contents of laboratory-raised fish as well as fish from the subtropical gyres were analyzed by Raman micro-spectroscopy (RMS) to identify polymer residues and any detectable persistent organic pollutants (POP). The goal was to access specific molecular information at the individual particle level in order to identify polymer debris in the natural environment. The identification process was aided by a laboratory generated automated fluorescence removal algorithm. Pacific Ocean trawl samples of plastic debris associated with fish collection sites were analyzed to determine the types of polymers commonly present. Subsequently, stomach contents of fish from these locations were analyzed for ingested polymer debris. Extraction of polymer debris from fish stomach using KOH versus ultrapure water were evaluated to determine the optimal method of extraction. Pulsed ultrasonic extraction in ultrapure water was determined to be the method of choice for extraction with minimal chemical intrusion. The Pacific Ocean trawl samples yielded primarily polyethylene (PE) and polypropylene (PP) particles >1 mm, PE being the most prevalent type. Additional microplastic residues (1 mm - 10 µm) extracted by filtration, included a polystyrene (PS) particle in addition to PE and PP. Flame retardant, deca-BDE was tentatively identified on some of the PP trawl particles. Polymer residues were also extracted from the stomachs of Atlantic and Pacific Ocean fish. Two types of polymer related debris were identified in the Atlantic Ocean fish: (1) polymer fragments and (2) fragments with combined polymer and fatty acid signatures. In terms of polymer fragments, only PE and PP were detected in the fish stomachs from both locations. A variety of particles were extracted from oceanic fish as potential plastic pieces based on optical examination. However, subsequent RMS examination identified them as various non-plastic fragments, highlighting the importance of chemical analysis in distinguishing between polymer and non-polymer residues.

Estimation of 5-fluorouracil-loaded ethylene-vinyl acetate stent coating based on percolation thresholds.

The drug percolation thresholds of 5-fluorouracil-loaded ethylene-vinyl acetate stent coatings were estimated to characterize their drug release behavior and mechanical properties. The stent coatings were prepared using 5-fluorouracil (5-FU) as antitumor drug and ethylene-vinyl acetate (EVA) as matrix forming material in different ratios. In vitro release assays were carried out exposing only one side of coating to pH 6.5 PBS. Based on the release profiles, the drug percolation thresholds were estimated as 0.21 of total porosity (corresponding to ca. 32%, w/w of the drug), which is in approximately agreement with the atomic force microscopy (AFM) result. Based on the coating tensible break strength and tear break strength data, the mechanical percolation thresholds of drug were obtained as 39.7+/-0.3 and 37.5+/-1.4% (w/w) of drug content, respectively.

SEM/EDS and optical microscopy analyses of microplastics in ocean trawl and fish guts.

Microplastic particles from Atlantic and Pacific Ocean trawls, lab-fed fish guts and ocean fish guts have been characterized using optical microscopy and SEM/EDS in terms of size, morphology, and chemistry. We assessed whether these measurements could serve as a rapid screening process for subsequent identification of the likely microplastic candidates by micro-spectroscopy. Optical microscopy enabled morphological classification of the types of particles or fibers present in the sample, as well as the quantification of particle size ranges and fiber lengths. SEM/EDS analysis was used to rule out non-plastic particles and screen the prepared samples for potential microplastic, based on their element signatures and surface characteristics. Chlorinated plastics such as polyvinyl chloride (PVC) could be easily identified with SEM/EDS due to their unique elemental signatures including chlorine, as could mineral species that are falsely identified as plastics by optical microscopy. Particle morphology determined by optical microscopy and SEM suggests the fish ingested particles contained both degradation fragments from larger plastic pieces and also manufactured microplastics. SEM images of microplastic particle surfaces revealed characteristic cracks consistent with environmental exposure, as well as pigment particles consistent with manufactured materials. Most of the microplastic surfaces in the fish guts and ocean trawls were covered with biofilms, radiolarians, and crustaceans. Many of the fish stomachs contained micro-shell pieces which visually resembled microplastics.

Treatments of paclitaxel with poly(vinyl pyrrolidone) to improve drug release from poly(ɛ-caprolactone) matrix for film-based stent.

Drug-loaded biodegradable films as a principal part of film-based stent were investigated for controlled drug delivery systems. In this study, solid dispersion technique, a pretreatment method of paclitaxel (PTX), was applied to prepare the PTX-loaded poly(ɛ-caprolactone) (PCL) films. Drug dissolution rates and characteristics of the poly(vinyl pyrrolidone) (PVP)/PTX solid dispersions (SDs) and physical mixtures (PMs) were investigated to show that the PVP/PTX SDs were successfully prepared before being incorporated in biodegradable films. Afterwards, the effect of the application of SDs on improving drug release behavior, weightlessness, crystalline states, and surface and internal morphologies of the films were studied. It was found that, the films with SDs showed a higher drug release rate than the films with PMs or pure PTX. In addition, the content of PVP in the SDs also had impact on drug release behavior: the more PVP in SDs, the faster the drug was released. According to the drug release test and weightlessness study, the possible drug release mechanism was put forward for the films with SDs. The application of solid dispersion technique showed a remarkable effect on improving drug release behavior for film-based biodegradable stent drug delivery systems.

Zero-order release of 5-fluorouracil from PCL-based films featuring trilayered structures for stent application.

A trilayered Poly(ε-caprolactone) (PCL)-based film with a coating layer (CL), a drug-storing layer (DSL) loaded with antitumor drug 5-Fluorouracil (5-FU) and a backing layer (BL) are presented for film-based stent application in malignant stricture or stenosis. V-C diffusion cells were used to investigate the drug permeability of the CL, while scanning electron microscopy (SEM) was employed for observing the microscopic architectures and morphologies. Drug release from the trilayered films exhibited a zero-order pattern, and the release process followed an 'outer-to-inner' pattern. The formation mechanism and influencing factors of the zero-order drug release pattern were in-depth elucidated, and factors affecting the drug release were also investigated. The reduction of initial drug loading in DSL slowed the drug release and diminished the zero-order release pattern. Drug permeability of the CL depended significantly on CL thickness, but not significantly on PCL molecular weight. Besides, the addition of PEG porogen in the CL accelerated the drug release by elevation of the drug permeability of CL, and the action mechanism of PEG was revealed by the PEG release test and SEM. The loading of 5-FU in the CL could lead to a two-phased release profile. This study revealed the potential of the trilayered film in controlled drug delivery to intraluminal tumor due to its highly tunable zero-order drug release.

Preparation, characterization and properties of partially hydrolyzed ethylene vinyl acetate copolymer films for controlled drug release.

In this study, partially hydrolyzed ethylene vinyl acetate (EVA) copolymers with three hydrolysis degrees (12.2%, 32.6% and 46.9%) were obtained by alkaline hydrolysis of EVA copolymer, characterized by Fourier-transform infrared spectroscopy (FTIR), (1)H NMR and gel permeation chromatography (GPC). Paclitaxel-loaded and drug-free films based on the partially hydrolyzed EVA copolymers were fabricated. The swelling behaviors, crystallinities, mechanical properties of the fabricated films were investigated, and the effects of hydrolysis degree, film thickness and drug loading dose on in vitro drug release from the films were also investigated. In vitro swelling study showed that the swelling of partially hydrolyzed EVA films was greater than the EVA film and the film with higher hydrolysis degree swelled more intensively. X-ray diffraction (XRD) results exhibited that the crystallinity of the polymer increased with increasing hydrolysis degree. In paclitaxel-loaded EVA film, a part of paclitaxel was in crystalline form; while in paclitaxel-loaded partially hydrolyzed EVA films, paclitaxel was distributed in amorphous form or molecularly dispersed. In the in vitro drug release test, the film with higher hydrolysis degree and smaller thickness released paclitaxel more quickly. With higher drug loading dose, the drug release rate was larger. The partially hydrolyzed EVA films were applied for drug delivery systems for the first time, and demonstrated to have great capability of controlling drug release thanks to the adjustable hydrolysis degree.

In vivo evaluation of 5-fluorouracil-containing self-expandable nitinol stent in rabbits: Efficiency in long-term local drug delivery.

This 5-fluorouracil (5-FU)-containing stent is fabricated by coating a film, composed of one 5-FU-containing ethylene-vinyl acetate (EVA) copolymer layer and one drug-free EVA protective layer, around a commercial self-expandable nitinol stent. The stents with various drug loadings were implanted into rabbit esophagus, and then 5-FU concentrations in the stent-touching and adjacent segments (including mucosa layer and muscle layer of each segment) of esophagus, serum, and liver were investigated throughout the experiment period. Quantitative analysis of 5-FU was performed by HPLC or LC-MS/MS, while the morphologies of esophageal mucosae by scanning electron microscopy (SEM). The results show that the 5-FU concentration in stent-touching esophageal tissue is overwhelmingly higher than that in serum or liver at all the investigation time points until 45 days. The 5-FU concentration in the stent-touching segment is higher than those in the other segments of esophagus, while the 5-FU concentration in mucosa layer is higher than that in muscle layer for the same segment. With the increase of drug loading, the drug concentrations in esophageal tissues and serum increase, and cellular desquamation of stent-touching epithelial surface become increasingly severe by SEM. Based on the results, the 5-FU-loaded esophageal stent operates long-term local drug delivery with great efficiency.

A type of esophageal stent coating composed of one 5-fluorouracil-containing EVA layer and one drug-free protective layer: in vitro release, permeation and mechanical properties.

A type of esophageal stent coating was investigated, which consists of one 5-fluorouracil (5-FU)-containing ethylene-vinyl acetate (EVA) copolymer layer and one drug-free EVA protective layer. The amount of 5-FU permeated through the protective layer (100 mum) is thousands of times lower than that of 5-FU released from the drug-loaded layer, indicating that the coating releases drug molecules in a unidirectional fashion. The barrier of the protective layer can be attributed to a tiny flux of 5-FU through the EVA film. In vitro release profiles of the stent coatings with various drug contents were investigated in pH 6.5 phosphate buffer solution. The results show that, the burst effect is not obvious for the coatings with 20-50% of 5-FU and the release profiles can be characterized by a first faster release rate phase followed by a decrease in release rate. The release data in the early and late stages can all be well fitted with zero-order kinetics, and the possible reasons for the release profiles were discussed. The rate of 5-FU permeation through porcine esophageal mucosa from the coatings can be adjusted by changing drug content of the coatings. The increase of drug content of the coatings significantly leads to the decrease of the maximum elongation, maximum tensible strength and maximum tear strength, and the increase of the modulus of elasticity. The coatings with 20-60% of drug attached to a stent can endure repeated binding and liberation via a stent introducer.