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Reducing the inflammatory response is a major goal in the therapy of rheumatoid arthritis (RA). Herein, we integrated palladium nanoparticles (Pd NPs) with selenium nanoparticles (Se NPs) and obtained a multiple nanosystem (Pd@Se-HA NPs) that could simultaneously scavenge hydroxyl radicals (⋅OH) and provide a photothermal effect. The Pd@Se-HA NPs were constructed by a simple self-assembly method in which Se NPs were electrostatically bonded to Pd NPs; hyaluronic acid (HA) was linked to the NPs by ester bonding to provide macrophage targeting ability. The experiments show that the combined therapy of eliminating ⋅OH with Se NPs and utilizing PTT with Pd NPs could effectively reduce the inflammatory response in macrophages more effectively than either individual NP treatment. In addition, the outer layer of HA could specifically target the CD44 receptor to enhance the accumulation of Pd@Se NPs at the lesion, further enhancing the therapeutic effect. After treatment for 15 days, the Pd@Se-HA NPs nearly eliminated the inflammatory response in the joints of mice in an induced RA model, and prevented joint damage and degradation.
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Malignant tumor has become an urgent threat to global public healthcare. Because of the heterogeneity of tumor, single therapy presents great limitations while synergistic therapy is arousing much attention, which shows desperate need of intelligent carrier for co-delivery. A core‒shell dual metal-organic frameworks (MOFs) system was delicately designed in this study, which not only possessed the unique properties of both materials, but also provided two individual specific functional zones for co-drug delivery. Photosensitizer indocyanine green (ICG) and chemotherapeutic agent doxorubicin (DOX) were stepwisely encapsulated into the nanopores of MIL-88 core and ZIF-8 shell to construct a synergistic photothermal/photodynamic/chemotherapy nanoplatform. Except for efficient drug delivery, the MIL-88 could be functioned as a nanomotor to convert the excessive hydrogen peroxide at tumor microenvironment into adequate oxygen for photodynamic therapy. The DOX release from MIL-88-ICG@ZIF-8-DOX nanoparticles was triggered at tumor acidic microenvironment and further accelerated by near-infrared (NIR) light irradiation. The
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This research aims to develop an UHPLC method, based on core-shell column(i.e. superficially porous particles), for simultaneous determination of eight isoflavonoids including formononetin,(6αR,11αR)-3-hydroxy-9,10-dimethoxypterocarpan, calycosin-7-O-β-D-glucopyranoside,(3R)-7,2-dihydroxy-3,4-dimethoxyisoflavone, calycosin, ononin,(6αR,11αR)-9,10-dimethoxypterocarpan-3-O-β-D-glucopyranoside, and(3R)-7,2-dihydroxy-3,4-dimethoxyisoflavan-7-O-β-D-glucopyranoside in Astragali Radix. The analysis was performed on an Agilent Poroshell EC-C_(18 )column(2.1 mm×100 mm, 2.7 μm) with 0.2% formic acid solution(A)-acetonitrile(B) as mobile phase for gradient elution. The flow rate was 0.5 mL·min~(-1), with column temperature of 40 ℃ and the wavelengths were set at 260 and 280 nm. According to the results, all calibration curves showed good linearity(R~2>0.999 8) within the tested concentration ranges. Both the intra-and inter-day precisions for 8 isoflavonoids were less than 0.80%, with the mean recovery at the range of 94.71%-104.6%. Thus, the newly developed UHPLC method using core-shell column owned the advantages in terms of rapid analysis, low column pressure and less solvent consumption, thus enabling the usage of conventional HPLC systems. Meanwhile, quantitative evaluation was carried out for 22 batches of commercial Astragali Radix. It has been found that great variations occurred for the content of the individual isoflavonoids among different batches; in contrast, the total content of total 8 isoflavonoids(>0.1%) was stable in most samples, indicating that it was reasonable to involve all isoflavonoids as the chemical markers for the quality control of Astragali Radix.
Subject(s)
Astragalus Plant , Chemistry , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal , Reference Standards , Flavones , Phytochemicals , Plant Roots , Chemistry , Quality ControlABSTRACT
Core-shell-type lipid-polymer hybrid nanoparticles (CSLPHNs) are composed by a biodegradable polymeric core coated with single or multiple layers of biomimetic lipids ,which combine the benefits of polymeric nanoparticles and lipo-somes .CSLPHNs have the advantages of small particle size ,high drug loading ,good biocompatibility and controlled release capability .It has wide applications as a novel drug delivery system .This review gives a brief introduction in characteristics , preparation methods and applications of CSLPHNs ,specifically summarizes the developments in the fields of ophthalmic drug delivery ,tumor therapy and medical diagnostic imaging .
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OBJECTIVE: To prepare smart & site-specific drug carrier for controlled release purpose and study the bio-compatibilities and release performance.METHODS: By using high pressure thermo-heat method in autoclave, superparamagnetic core was obtained and further coated by SiO2 and MCM-41, therefore the “core-shell” structure was formed. To make the carrier “smart” and thus responsive to stimuli which was light in this research, the tunnels of the molecular sieve were grafted with gating molecules, 4,5-diazafluoren-9-one (indicated in the paper as DAFO). For bio-compatibilities testing, MTT in-vitro experiment was conducted. Cytarabine was used as test drug to preliminarily evaluate the controlled release performance of the drug carrier in vitro.RESULTS: The Fe3O4 nano-particles synthesized via high-pressure hydro-thermo procedure exhibited superparamagnetic with mean diameter of 280 nm. After SiO2 & molecular sieve coating steps and ligand grafting steps, the particles grew to 540 nm. The sub-structure of the carrier was confirmed by scanning/transmission electron microscope(SEM & TEM) and nitrogen adsorption/desorption. Our “smart” carrier was able to be guided to the sites or organs with magnetic field and more importantly it was able to unload drug molecules under 510 nm light irritation that could flip the gating-molecule. Furthermore, the drug carrier illustrated bio-compatibility and showed obvious cytotoxicity.CONCLUSION: The novel nanocomposites developed in this study can be used as targeted drug carrier.
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Metallothionein ( MT) is a low-molecular-weight protein with high inducibility and binding ability with metal ions. Therefore, MT is often regarded as an important biomarker for assessment of heavy metal pollution in water environment. But the traditional process of its enrichment and identification is time-consuming and complicated. Herein, we prepared a core-shell nanoparticle, gold-coated iron oxide nanoparticles ( Fe3O4@Au NPs) . The nanoparticle possessed the advantages such as fast response to magnetic fields and optical properties attributing to Fe3O4and Au nanoparticles separately. Fe3O4@Au nanoparticles were used to enrich MT simply through Au-S interaction, and the purified proteins were determined by matrix assisted laser desorption ionization time-of-flight mass spectrometry ( MALDI-TOF/MS) . The results in this work showed that the Fe3O4@Au nanoparticles could directly enrich MT from complex solutions and the detection limit could be down to 10 fg/mL.
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Simple, sensitive, rapid and stability indicating ultra high efficiency RP-HPLC method was developed and validated for analysis of Tranylcypromine sulphate in bulk drug and in tablet dosage forms. Well- resolved peaks of target analyte and its degradation products were achieved on a Kinetex® column (75 mm x 4.6 mm ID) 2.6 μm at 30 °C, using simple isocratic mobile phase of acetonitrile - orthophosphoric acid 0.1 % (10: 90, v/v). The flow rate was 1.0 mL/min and the detection was performed at 220 nm. The retention time of the drug was 2 min while for the reported method was 6.7 min. The method was validated according to International Conference on Harmonization (ICH) guidelines. Tranylcypromine was subjected to the stress conditions of hydrolytic acidic, basic, oxidative, and photolytic degradation. The assay was linear over the concentration range of 3-150 μg mL-1 and the correlation coefficient was 1. The RSD% of inter and intraday precision was less than 1 %. The % recoveries were found to be 100.58 % proved that the proposed method is sufficiently accurate and precise. The method distinctly separates the drug from its degradation products within 2 min and total run time of 8 min.
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The core-shell nanopaticles of Au@polyvinyl-pyrrolidone ( PVP) with uniform size and controllabe shell-thickness were prepared by hydrothermal method. The core-shell nanoparticles could be assembled to be the monolayer array on Si substrate relying on the dispersion of core-shell nanoparticles arising from PVP shell. The malachite green ( MG ) absorbed by H-bond could be detected on the array under the electromagnetic enhancement of inner-core Au nanoparticles. Under the conditions of the optimum shell-thickness of Au@PVP and the appropriate absorbed time of MG, the detection of MG could be realized in the linear range from 1 × 10-10 mol/L to 1 × 10-5 mol/L with the correlation coefficient ( R2 ) of 0. 98. The detection limit was 10-12 mol/L. This method was applied to the determination of MG in tilapia fish fillets of Xiagang market. No MG was found in this real sample. The spiked recoveries of the sample ranged from 70. 8% to 126. 0%. This method is simple and accurate, and can be used for detection of MG in the fish.
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BACKGROUND: This study describes a novel analytical method for simultaneously determining sarpogrelate and its metabolite (M-1) in human plasma, using liquid chromatography coupled with tandem mass spectrometry, with electrospray ionization in the positive ion mode. METHODS: Sarpogrelate, M-1, and labeled internal standard (d3-sarpogrelate) were extracted from 50 microL of human plasma by simple protein precipitation. Chromatographic separation was performed by using a linear gradient elution of a mobile phase involving water-formic acid (99.9:0.1, v/v) and acetonitrile-formic acid (99.9:0.1, v/v) over 4 min of run time on a column, with a core-shell-type stationary phase (Kinetex C18, 50 mm x 2.1 mm i.d., 2.6-microm particle size, Phenomenex, USA). Detection of the column effluent was performed by using a triple-quadruple mass spectrometer in the multiple-reaction monitoring mode. RESULTS: The developed method was validated in human plasma, with lower limits of quantification of 10 ng/mL for sarpogrelate and 2 ng/mL for M-1. The calibration curves of sarpogrelate and M-1 were linear over the concentration ranges of 10-2,000 and 2-400 ng/mL, respectively (R2>0.99). The carry-over effect, precision, accuracy, and stability of the method met the criteria for acceptance. CONCLUSIONS: A simple, fast, robust, and reliable analytical method was successfully developed and applied to the high-throughput determination of sarpogrelate and its metabolite in real plasma samples in a pharmacokinetic study of healthy subjects.
Subject(s)
Humans , Calibration , Chromatography, Liquid , Mass Spectrometry , Particle Size , Plasma , Tandem Mass SpectrometryABSTRACT
Background Cyclodextrin glucanotransferase (CGTase) from Amphibacillus sp. NPST-10 was covalently immobilized onto amino-functionalized magnetic double mesoporous core-shell silica nanospheres (mag@d-SiO2@m-SiO2-NH2), and the properties of the immobilized enzyme were investigated. The synthesis process of the nanospheres included preparing core magnetic magnetite (Fe3O4) nanoparticles, coating the Fe3O4 with a dense silica layer, followed by further coating with functionalized or non-functionalized mesoporous silica shell. The structure of the synthesized nanospheres was characterized using TEM, XRD, and FT-IR analyses. CGTase was immobilized onto the functionalized and non-functionalized nanospheres by covalent attachment and physical adsorption. Results The results indicated that the enzyme immobilization by covalent attachment onto the activated mag@d-SiO2@m-SiO2-NH2, prepared using anionic surfactant, showed highest immobilization yield (98.1%), loading efficiency (96.2%), and loading capacity 58 µg protein [CGTase]/mg [nanoparticles]) which were among the highest yields reported so far for CGTase. Compared with the free enzyme, the immobilized CGTase demonstrated a shift in the optimal temperature from 50°C to 50-55°C, and showed a significant enhancement in the enzyme thermal stability. The optimum pH values for the activity of the free and immobilized CGTase were pH 8 and pH 8.5, respectively, and there was a significant improvement in pH stability of the immobilized enzyme. Moreover, the immobilized CGTase exhibited good operational stability, retaining 56% of the initial activity after reutilizations of ten successive cycles. Conclusion The enhancement of CGTase properties upon immobilization suggested that the applied nano-structured carriers and immobilization protocol are promising approach for industrial bioprocess for production of cyclodextrins using immobilized CGTase.
Subject(s)
Bacillaceae/enzymology , Enzymes, Immobilized , Glucosyltransferases/isolation & purification , Glucosyltransferases/metabolism , Solvents/isolation & purification , Temperature , Porosity , Silicon Dioxide , Cyclodextrins , Nanospheres , Glucosyltransferases/biosynthesis , Hydrogen-Ion ConcentrationABSTRACT
OBJECTIVE: To introduce the basic mechanism of coaxial-electrospraying and influencing parameters of preparation process, and review the recent development of preparing core-shell nanoparticles by using coaxial-electrospraying.
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Objective: To prepare and characterize Indigo Naturalis-Alumen (INA) composite particles with core-shell structure based on the particle design principle. Methods: The preparation time of shell particles and composition time of composite particles were studied using particle size and contact angle as evaluation indexes, respectively. Four kinds of powders including Indigo Naturalis fine powder, Alumen fine powder, INA mixture, and INA composite particles were prepared respectively; Their properties such as particle size, powder color, microstructure, distribution of surface elements, and crystal structure were compared, so as to study the core-shell structure of composite particles. Results: During the period of the preparation, the shell particles were added into vibromill and ground for 17 min separately, and then the core particles were added and ground with shell particles together for 5 min. There was no difference between the composite particles and shell particles in surface wettability. The median diameter (d0.9) of the composite particles was 32.818 μm, which was much smaller than that of the mixture. The color and surface elements distribution were highly similar to the shell particles. In SEM, the microstructure that the surface of big particles coated with a large number of small particles could be observed. In X-ray diffractogram, many characteristic absorption b ands of the core particles were disappeared or decreased. Conclusion: INA composite particles with core-shell structure are prepared successfully, the surface properties are similar to the shell particles and are different with the core particles.
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The advent of superficially porous particles (SPPs) for packed HPLC columns has changed the way that many practitioners have approached the problem of developing needed separations. The very high efficiency of such columns, combined with convenient operating conditions, modest back pressures and the ability to use conventional HPLC instruments has resulted in intense basic studies of SPP technology, and widespread applications in many sciences. This report contains an overview of the SPP technology first developed in 2006 by Advanced Materials Technology, Inc., for sub-3-mm particles, then expanded into a family of SPP products with different particle sizes, pore sizes and other physical parameters. This approach was designed so that each particle of the family could be optimized for separating a particular group of compounds, usually based on solute size.
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Employing resveratrol as template molecule, acrylamide as functional monomer and ethyleneglycol dimethacrylate as cross-linkers, a core-shell resveratrol imprinted microspheres was prepared based on the surface of SiO_2 with a surface imprinting technique.The molecularly imprinted microsphere was characterized by infrared spectroscopy and scanning electron microscopy, and the results showed that the surface grafting of molecularly imprinted polymer-shell particle on SiO_2 was successful and the particles were evenly distributed.High performance liquid chromatography was also used to investigate the imprinted microsphere adsorption per formance, and the results showed that the imprinted microsphere exhibited good recognition performance.The maximum adsorption capacities were Q_(maxl)=9.087 mg/g and Q_(max2)= 13.80 mg/g by the model of Scatchard analysis.The imprinted micospheres was applied to separate resveratrol from the extraction of rhizoma polygoni cuspidate successfully.
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Recently, more and more public attention has been paid to nanomaterials in various fields. Especially, the preparation methods of core/shell nanoparticles have been drastically updated and developed. There exists great application prospect for the development of biosensing core/shell nanoparticles. This paper emphatically introduced the operation principle, preparation methods of biosensing core/shell nanopaticles and the latest application progress in electrochemical biosensor, optical biosensor and piezoelectric crystal biosensor.
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OBJECTIVE:To prepare core-shell nanocapsules loading nicardipine hydrochloride and to investigate its pharmaceutical characteristics. METHODS: Core-shell nanocapsules were prepared using layer-by-layer electrostatic self-assembly technique. The indexes including the shape and particle size and the loaded drug amount of the nanocapsules were evaluated, and its accumulative release rates in artificial gastric juice and intestinal juice were computed and compared with those of its crude drug. RESULTS: The results showed that the nanocapsules were spherical with a mean particle size of 200 nm and a maximum loaded drug amount of 2.512%. The drug release rate within 12 h reached 18.64% in artificial gastric juice and 70% in artificial intestinal juice, whereas within 3 h the drug release rate of its crude drug in artificial intestinal juice reached 87%. CONCLUSIONS: The prepared core-shell nanocapsules containing nicardipine hydrochloride had a good pharmaceutical property.