Preparation and Characterization of pH-Sensitive Polyvinyl Alcohol Hydrogel for Cancer Therapy

Hydrogel has emerged as an excellent carrier platform for smart drug delivery and effective cancer treatment due to its high water content, good biocompatibility and sufficient mechanical properties. In this work,the DOX-loaded polyvinyl alcohol（ PVA）hydrogel was prepared by freeze-thawing technique. The swelling test and the mechanical properties of the pure PVA hydrogels were performed. In addition, the in vitro drug release profiles were examined and the in vitro antitumor efficiency against He La cells was also estimated. The results indicated that the resulting PVA hydrogels contained significant amounts of water and possessed good mechanical properties,and DOX-loaded PVA hydrogel exhibited a sustained and p H-responsive DOX release. The MTT assays also demonstrated that the released DOX could effectively inhibit the proliferation of He La cells. Thus,the cross-linked PVA hydrogel can be further developed as a promising platform for cancer therapy.     

Cupric ion release and cytotoxicity for Yuangong Cu-IUDs and the release behavior of indomethacin for medicated 220 Cu-IUD

These years Yuangong copper-bearing intrauterine devices （Cu-IUDs） have been used because of less side effects in use. The corrosion of copper is essential to the success of contraception, and the release behavior of indomethacin from medicated Cu-IUD is related to its therapeutic effect. In this study, analytical methods were established to investigate the release behavior of cupric ion of three kinds of Yuangong Cu-IUDs and indomethacin of medicated Yuangong 220 Cu-IUD. Cu-IUDs were incubated in simulated uterine solution （SUS）. The concentrations of cupric ion and indomethacin were analyzed by flame atomic absorption spectrometer （FAAS） for 60 days and UV/vis -3310 spectrophotometer for 60 days, respectively. The morphology of copper after corrosion was characterized by SEM. In addition, we detected cytotoxicity by MTT of L929 mouse fibroblasts cells caused by extracts of the three Yuangong Cu-IUDs. The release behavior of cupric ion for three kinds of Yuangong Cu-IUDs was biphasic, which consisted of the initial burst release and then slow and constant release. In vitro release experiment confirmed a biphasic release of indomethacin from Yuangong 220. The copper wire of Yuangong Cu-IUDs showed uneven corrosion. The RGR value of Yuangong 365 Cu-IUD was smaller than that of medicated Yuangong 220 Cu-IUD and RGR value of medicated Yuangong 220 Cu-IUD was smaller than that of Yuangong 300 Cu-IUD. The cupric ion release and indomethacin release showed biphasic. Indomethacin increased the cupric ion release rate and might diminish the adverse effects caused by burst release of cupric ion. The toxicity grade of these three Yuangong Cu-IUDs was 4. We should canvass the adverse events of Cu-lUDs based on practical experiments, and try our best to reduce the toxicity of Cu-lUDs.     

Preparation and characterization of a chitosan-based low-pH-sensitive intelligent corrosion inhibitor

A chitosan (CS)-based low-pH-sensitive intelligent corrosion inhibitor was prepared by loading a pH-sensitive hydrogel with benzotriazole (BTA); the pH-sensitive hydrogel was synthetized by crosslinking CS with glutaraldehyde (GTA). Analysis by Fourier- transform infrared (FT–IR) spectroscopy showed that Schiff reactions occurred between amino and aldehyde groups. The swelling ability of the hydrogel was investigated using a mass method, and it was observed to swell more in an acidic environment than in an alkaline environment. The hydrogel’s loading capacity of BTA was approximately 0.377 g·g-1, and its release speed was faster in an acidic environment than in an alkaline environment because of its swelling behavior. The corrosion inhibition ability of the intelligent inhibitor was tested by immersion and electrochemical methods. The results showed that after 4 h of immersion, the polarization resistance (R4) value of copper with the intelligent inhibitor was approximately twice of that of copper with BTA, indicating that the intelligent inhibitor could effectively prevent copper from corroding.     

Glycyrrhetinic acid-modified nanoparticles for drug delivery: Preparation and characterization

In this work, glycyrrhetinic acid-modified chitosan （mGA-suc-CTS） used as liver targeted carrier for drug delivery, was prepared via hemisuccinate as a bridged group. The structure of the product was confirmed by IR and NMR methods and the degree of substitution （DS） of glycyrrhetinic acid groups was estimated via elemental analysis. Nanoparticles were formed by ionic gelation methold. The drug-loading and release behavior of the nanoparticles were investigated using BSA as the model drug. The results indicated that the carrier with a highest DS of 5.19% could be got and the DS was controlled by changing reaction temperature or feed ratio. BSA could be entrapped into the nanoparticles with the drug-loading ratio of 26.3% and the encapsulation efficiency of 81.5%. A sustained release over an 11-day period was observed in pH 7.4 in vitro.     

A new drug carrier: Magnetite nanoparticles coated with amphiphilic block copolymer

This paper reports on the synthesis and characterization of 4 nm magnetite nanoparticles coated with amphiphilic block copolymers of poly(ethyl methacrylate)-b-poly(2-hydroxyethyl methacrylate) (PEMA- b-PHEMA) by surface-initiated atom transfer radical polymerization (ATRP), which can act as new po-tential carriers for hydrophobic targeted drug delivery. Vibrating sample magnetometer analysis indi-cated that the magnetite nanoparticles were superparamagnetic at room temperature. Thermogravim-etric analysis (TGA) was applied to studying the property of surface of magnetite nanoparticles, and the surface density of macromolecules was calculated. The grafting density of oleic acid, BrMPA and PEMA was 5.8, 3.9, 0.16 chain/nm2 respectively, which indicates that the initiation efficiency decreases due to the influence of large space of oleic acid molecules. In vitro progesterone and (-)-isoproterenol hy-drochloride release in phosphate buffered saline (PBS) at pH 7.0 and 37℃ was conducted in order to demonstrate the function of drug loading and release. The results showed that the amount of drug carried into the core-shell Fe₃O₄@PEMA-b-PHEMA depends on the length of hydrophobic segment of block copolymer. The release of progesterone (37% after 22 h in our previous work) was compared with the release of (-)-isoproterenol hydrochloride (80% after 50 min), demonstrating that the strong hy-drophobic interaction between hydrophobic segment and drug can effectively control the release of hydrophobic drugs.     

Folate-Polyethyleneimine Grafted Polymer Multilayer Hollow Microcapsules as a Slow-Release Carrier of Doxorubicin

A novel biodegradable and biocompatible multilayer hollow microcapsules,modified by folate-conjugated polyethyleneimine(PEI),as targeted and sustained release carriers of doxorubicin(DOX),were successfully synthesized using the sequential layer-by-layer electrostatic assembly technique from the sacrificial microtemplates(CaCOj/CMC,spherical,1.7 μm) with chitosan(CS) and sodium carboxymethyl cellulose(CMC) as the polycation and polyanion polyelectrolyte.Scanning electron microscope(SEM) observation showed that the diameter of the seven assembly multilayer microparticles was about 2.0 μm with relatively regular sphere.After the microparticle cores was removed by complexation with ethylene diamine tetraacetic acid(EDTA) for calcium ions,the range of 200- 300 nm wall thickness of microcapsules was built,and it made the forming microcapsules to be stable.Thermogravimetric analysis confirms the deposition and modification total amount of polymer on the microtemplates is about33.5%.The assembly microparticles were modified by introducing PEI,and the grafting rate of folate could reach 20.0%.It was 4times that of traditional method.The high grafting rate helped to improve targeting action of microcapsules.The deposition of DOX was prominent and the encapsulation efficiency was 96.9%,and the plateaued release of loaded drug reached 78%in pH 7.4 buffer solution,and then in pH 5.7 showed significantly a slow release.     

Of pH and Eh on release of nitrogen and phosphorus from sediments of West Lake

The effects of pH and Eh on release of nitrogen and phosphorus from sediments of West Lake under different conditions were investigated by simulation test. Results showed that the net flux of NH4^ -N re-lease from sediments increased with pH, but NO3^- -N showed negative-going release at all tested pH levels.The net flux of NH4^ -N release from sediments was higher under anaerobic or aerobic condition of the overly-ing water, but only under aerobic condition would net release of NO3^- -N occur. It was also shown that phos-phorus released was mainly in its inorganic form, higher pH and anaerobic conditions of overlying water greatly stimulated release of phosphorus. In situ measurement at several West Lake locations indicated that sediment resuspension induced by boat propeller stimulated nutrients release from sediment into overlying water.     

Compressive fatigue behavior and failure evolution of additive fiber-reinforced cemented tailings composites

The ordinary cemented tailings backfill(CTB)is a cement-based composite prepared from tailings,cementitious materials,and water.In this study,a series of laboratory tests,including uniaxial compression,digital image correlation measurement,and scanning electron microscope characteristics of fiber-reinforced CTB(FRCTB),was conducted to obtain the uniaxial compressive strength(UCS),failure evolution,and microstructural characteristics of FRCTB specimens.The results show that adding fibers could increase the UCS values of the CTB by 6.90%to 32.76%.The UCS value of the FRCTB increased with the increase in the polypropylene(PP)fiber content.Moreover,the reinforcement effect of PP fiber on the CTB was better than that of glass fiber.The addition of fiber could increase the peak strain of the FRCTB by0.39%to 1.45%.The peak strain of the FRCTB increased with the increase in glass fiber content.The failure pattern of the FRCTB was coupled with tensile and shear failure.The addition of fiber effectively inhibited the propagation of cracks,and the bridging effect of cracks by the fiber effectively improved the mechanical properties of the FRCTB.The findings in this study can provide a basis for the backfilling design and optimization of mine backfilling methods.     

Segmentation algorithm of complex ore images based on templates transformation and reconstruction

Lots of noises and heterogeneous objects with various sizes coexist in a complex image, such as an ore image; the classical image thresholding method cannot effectively distinguish between ores. To segment ore objects with various sizes simultaneously, two adaptive windows in the image were chosen for each pixel; the gray value of windows was calculated by Otsu’s threshold method. To extract the object skeleton, the definition principle of distance transformation templates was proposed. The ores linked together in a binary image were separated by distance transformation and gray reconstruction. The seed region of each object was picked up from the local maximum gray region of the reconstruction image. Starting from these seed regions, the watershed method was used to segment ore object effectively. The proposed algorithm marks and segments most objects from complex images precisely.     

Dialdehyde starch nanoparticles as antitumor drug delivery system: An in vitro, in vivo, and immunohistological evaluation

Sustaining the release of therapeutic nanoparticles in a cell-, tissue-, or disease-specific manner is a potentially powerful technology. A new drug carrier-dialdehyde starch nanoparticle (DASNP) that can sustain the loading and release of 5-fluorouracil (5-Fu) antitumor drug is reported in this study. IR spectrophotometer and 1H NMR confirmed the formation of aldehyde groups, and scan electron microscope determinations showed that the dialdehyde starch nanoparticles obtained had an average diameter of 90 nm. 5-Fu, the model drug, was conjugated into nanoparticles by aldehyde groups. These 5-Fu-binding nanoparticles significantly enhanced breast cancer cell (MCF-7) inhibition in vitro compared with free 5-Fu. After subcutaneous 0 injection in the breast tumor-loaded rats, 5-Fu-DASNP exhibited remarkable tumor-inhibitory efficacy determined by measuring tumor weight in vivo. The tumor inhibition of 5-Fu-DASNP was 61%±6%, whereas that of free 5-Fu was only 42%±4%. Bcl-2/Bax immunohistochem-istry studies indicated that 5-Fu-DASNP remarkably induced tumor tissue necrosis. These results demonstrated that the DASNP prepared in this work is a potentially effective drug carrier.     

Dialdehyde starch nanoparticles： Preparation and application in drub carrier

Dialdehyde starch nanoparticles (DASNP) were prepared by the redox reaction of NaIO4 and starch in water-in-oil microemulsion. IR spectrum showed that DASNP had aldehyde groups, and quantitative alkali consumption showed that its dialdehyde content was about (50±5)%. The average diameter of DASNP determined by SEM was about 100 nm. TGA-DTA showed that its thermal stability was better than starch nanoparticle (StNP) and dialdehyde starch (DAS). Its low biological toxicity was detected by cell experiment. Also the best mass ratio of doxorubicin (DOX) to combined DASNP detected by UV-VIS was 15 : 1, and the product was effective for controlled release of DOX. The cell experiment showed that the drug-carrier particle (DOX-DASNP) can release DOX for a long time and strengthened the effect of the anticancer drug. This work demonstrates that the DASNP, which has good thermal stability, small particle size, low biological toxicity, and slowly anticancer drug-releasing to strengthen drug effect, is a potentially useful carrier for anticancer drug.     

Hydroxyl radical electrochemically generated with water as the complete atom source and its environmental application

The most reactive hydroxyl radical （OH） was generated by electrochemical approach with safe water as the complete atom source. The direct evidence for OH formation was obtained by electron spin resonance method. The powerful OH electrochemically generated could effectively degrade organic pollutants and reduce the toxicity of wastewater. Electrochemical disinfection by OH was considerably efficient even without the aid of active chlorine. Bacteria inactivation of 99.99% was achieved for contact time of 30 min and current density of 5 mA·cm^-2, In comparison with active chlorine, OH is rather attractive as a promising environmentally benign disinfectant and opens a new route for microbial inactivation.     

Enhanced Biological Phosphorus Removal in Anaerobic/Aerobic Sequencing Batch Reactor Supplied with Glucose as Carbon Source

Phosphorus removal performance in an aerobic/aerobic sequencing batch reactor （SBR） supplied with glucose as carbon source was investigated. It was found that there was no phosphate release concomitant with the storing of poly-β-hydroxyalkanoate （PHA） during the anaerobic phase. Whereas, glycogen was soon built up followed by rapid consumption, at the same time, glucose was depleted rapidly. Based on the analysis of different fractions of phosphorus in activated sludge, the relative ratio of organically bound phosphorus in sludge changed at the end of anaerobic and aerobic phases. The ratios were 45.3% and 51.8% respectively. This showed that the polyphosphate broke down during the anaerobic phase to supply part of energy for PHA synthesis. The reason why there was no phosphate release might be the biosorption effect of extracellular exopolymers （EPS）. It was also proved by the analysis of EPS with scanning electron microscopy （SEM） combined with energy dispersive spectrometry （EDS）. The phosphorus weight percentage of EPS at the end of anaerobic phase was 9.22%.     

Glycyrrhizic Acid-Targeted Carbon Nanotube Nanocomposites with Polyethylenimines-Mediated for Cancer Drug Delivery

In order to enhance the efficiency and specificity of anticancer drug delivery and realize intelligently controlled release,a new multi-functional nanoparticle drug carrier was synthesized.The drug carrier was prepared by functionalizing multi-walled carbon nanotubes(MWCNTs) with polyethylenimines(PEI),fluorescein isothiocyanate(FITC) and glycyrrhizic acid(GL).After detailed characterization,doxorubicin(DOX) was loaded onto the obtained MWCNT composites through π-π stacking interactions.The drug loading capacity of the GL-functionalized material was up to 92%,and the release behavior was significantly pH-sensitive.Release at pH = 5.8(typical of the tumor cell microenvironment) was much more rapid and reached a greater extent than release under normal physiological conditions(pH = 7.4).The modified MWCNTs had high biocompatibility with the liver cancer cell line SMMC-7721,but were able to induce cell death after 24 h incubation if loaded with DOX.Tests with shorter incubation time(2 h) were undertaken to investigate the selectivity of the MWCNT composites,showed that the nanocomposites could specifically target cancer cells.The above results suggest that the functionalized carbon nanotubes-based material has potential applications for targeted delivery and controlled release of anticancer drug.     

Effects of protonation and deprotonation on the reactivity of quinolone: A theoretical study

Quinolones are the subject of much research as antibacterial compounds and as a new class of antitumor agents.The protonation(P) and deprotonation(D) sites and conformations of quinolone were investigated.The proton affinity(PA) on each of the possible sites in 4-oxo-1,4-dihydroquinoline has been calculated by the restricted Hartree-Fock(HF) and density functional theory(DFT) methods with the basis set 6-311G**.The O-site of protonation was found to be strongly favored over the N-site for the studied compound in the gas phase.Deprotonation takes place in quinolone by detachment of the N-H and COOH protons.The PA of the simple quinolone molecule was used to characterize quinolone reactivity with DNA binding sites.The relative stabilities of the syn and anti conformations were investigated at the B3LYP/6-311G** level of theory;the syn form was shown to be slightly more stable.Its conformation seems to be intrastabilized by hydrogen-bonds consisting of a hydroxyl proton with the O10 atom as the acceptor.We computed and discussed the charge-density distribution and electrostatic potential to explain the reactivity of quinolone.     

Affinity ultrafiltration of DNA topoisomerases-targeted compounds determined with HPLC／ESI-MS for drug candidate screening

A method of screening assay is demonstrated. The approach is based on the affinity of antitumor candidates for topoisomerases. In this method, antitumor candidates are fished out using topoisomerases as targets. Traditional analysis of complex compounds typically encounters signal suppression due to the relatively low concentrations, but enzyme-affinity screening for the active compounds can effectively concentrate the desired analysts into a small volume of high concen-tration. Active compounds are separated from non-affinity compounds by ultrafiltration. The molecules-enzymes complexes that are retained on the filter are subsequently separated by acidification to obtain the topoisomerases-affinity compounds for analysis on High Performance Liquid Chromatography coupled with electrospray ionization mass spectrometric detec-tion (ESI-MS). This enzyme-affinity based screening assay provides a highly specific and efficient method that can directly screen, identify, and acquire drug candidates thus improving the accuracy and speed of high-throughput screening activities.     

Rational groundwater table indicated by the ecophysiological parameters of the vegetation： A case study of ecological restoration in the lower reaches of the Tarim River

The eco-physiological response and adaptation of Populus euphratica Oliv and Tamarix ramosissima Ldb during water release period were investigated. Nine typical ＇areas and forty-five transects were selected along the lower reaches of Tarim River. The groundwater table as well as plant performance and the contents of proline, soluble sugars, and plant endogenous hormone （ABA, CTK） in leaves were monitored and analyzed. The groundwater table was raised in different areas and transects by water release program. The physiological stress to P. euphratica and T. ramosissima had been reduced after water release. Our results suggested that the groundwater table in the studied region remained at -3.15 to -4.12 m, theproline content from 9.28 to 11.06 （mmol/L）, the soluble sugar content from 224.71 to 252.16 （mmol/L）, the ABA content from 3.59 to 5.01 （ng/g FW）, and the CK content from 4.01 to 4.56 （ng/g FW）, for the optimum growth and restoration of P. euphratica indicated by the plant performance parameters and the efficiency of water application was the highest. The groundwater table in the studied region remained at -2.16 to -3.38 m, the proline content from 12.15 to 14.17 （mmol/L）, the soluble sugar content from 154.71 to 183.16 （mmol/ L）, the ABA content from 2.78 to 4.86 （ng/g FW）, and the CK content from 3.78 to 4.22 （ng/g FW）, for the optimum growth and restoration of T. ramosissima indicated by the plant performance parameters and the efficiency of water application was the highest. The rational groundwater table for the restoration of vegetation in the studied region was at -3.15 to -3.38 m.     

Tussah Silk Fibroin Porous Scaffolds Prepared with a Mild Self-assembly Process for Controlled Drug Release

Besides excellent biodegradability and biocompatibility,a useful tissue engineering scaffold should provide favorable surface properties,outstanding mechanical strength and controlled drug release property. In this paper,a mild process to prepare porous tussah silk fibroin（ TSF） scaffolds from aqueous solution was described. The n-butanol was used to control the self-assembly of tussah silk. The scaffolds with different TSF concentrations and the same volume showed differences in pore size and distribution. The maximum porosity of the poprepared porous scaffolds was 80% in this paper. And the pore size of the prepared porous scaffolds with different concentrations was between 10μm and 230 μm. X-ray diffraction（ XRD） analysis revealed that amorphous TSF was crystallized to β-sheet secondary structure upon gelatin. The TSF scaffolds for controlled drug release was studied and the result showed that the time of drug release was significantly longer. The produced TSF scaffolds with sustained drug release have potential application in tissue engineering.     

Preparation,Characterization, and Antitumor Efficacy of,Camptothecine-Loaded Hydroxyapatite / Poly （lactic-co,glycolic acid ） Composite Nanofibers via Electrospinning

In the past decade, various medicated nanofibrous scaffolds have been developed as effective drug delivery systems for postsurglcal cancer treatment. In this study, hydroxyapatite nanoparticles （HANPs） were used as carriers to load an anticancer （CPT）, and the CPT-Ioaded HANPs （CPT @HANPs） was then incorporated into poly（ lactic-co.glycolic acid） （PLGA） nanofibers via electrospinning. Thus fabricated medicated nanofibrous mats （ PLGA /CPT @ HANPs） were characterized by field emission scanning electron microscope （FESEM）, transmission electron microscope （TEM）, attenuated total reflection Fourier transform infrared spectroscopy （ATR-FTIR） and X-ray diffraction （XRD）. The release prof＇des of CPT from the medicated electrospun mats were obtained and their in vitro anticancer efficacy against HeLa cells was also evaluated. The results showed that the CPT was successfully loaded onto the surface of HANPs, and the prepared electrospun mats exhibited a homogeneous and continuous morphology. Furthermore, the loaded CPT exhibited a sustained release behavior from the nanoflbrous mats and the released CPT showed a long-term anticancer efficacy against HeLa cells. Therefore, the prepared medicated electrospun mats may be served as an effective drug delivery device for local antitumor treatment.