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In this study, the effect of limestone content on the mechanical performance and the heat of hydration of ordinary Portland cement (OPC) was investigated. Changes in the phase assemblage were analyzed through XRD and thermodynamic modeling. The purpose of the study was to identify the optimal limestone content in OPC. As a result of the experiment, all samples were found to have equal fluidity. Increasing the limestone content accelerated the hydration of the cement before approximately 13 h and shortened the setting time due to the acceleration of the initial hydration reaction. The compressive strength of the cement mortar showed a dilution effect, with lower compressive strength compared to the reference sample at an early age, but it gradually recovered at a later age. This is because, as shown in the XRD and thermodynamic modeling results, the carboaluminate phases formed due to the chemical effect of limestone contributed to the development of compressive strength. As a result, within the scope of this study, it is believed that maintaining the limestone content in OPC within 10% is optimal to minimize quality degradation.
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We have examined whether the copper reduction slag (CRS) generated after recovering valuable metals from copper slag (CS) by reduction process can be used as supplementary cementitious materials (SCMs). According to the test results, the Cu secondary slag with low Fe, Cu, and heavy metal contents had a suitable oxide composition for using as a SCM. CRS showed better grinding efficiency than that of ground blast furnace slag (GGBS). Ground CRS contributed to the formation of tobermorite under autoclaved curing conditions. The compressive strength of CRS mortar replacing 50 % of OPC generated 93 % of that of the OPC mortar. Based on the results of this study, we found that the CRS has highly appropriate engineering characteristics for using as SCMs for concrete. In addition, it is judged that the method of using secondary slag as a material for precast concrete produced under hydrothermal conditions can greatly contribute to the construction process of buildings by securing mechanical performance.
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A diverse population of avian influenza A viruses (AIVs) are maintained in wild birds and ducks yet the zoonotic potential of AIVs in these environmental reservoirs and the host-virus interactions involved in mammalian infection are not well understood. In studies of a group of subtype H1N1 AIVs isolated from migratory wild birds during surveillance in North America, we previously identified eight amino acids in the polymerase genes PB2 and PB1 that were important for the transmissibility of these AIVs in a ferret model of human influenza virus transmission. In this current study we found that PB2 containing amino acids associated with transmissibility at 67, 152, 199, 508, and 649 and PB1 at 298, 642, and 667 were associated with more rapid viral replication kinetics, greater infectivity, more active polymerase complexes and greater kinetics of viral genome replication and transcription. Pathogenicity in the mouse model was also impacted, evident as greater weight loss and lung pathology associated with greater inflammatory lung cytokine expression. Further, these AIVs all contained the avian-type amino acids of PB2-E627, D701, G590, Q591 and T271. Therefore, our study provides novel insights into the role of the AIV polymerase complex in the zoonotic transmission of AIVs in mammals.
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Subtipo H1N1 del Virus de la Influenza A , Virus de la Influenza A , Gripe Aviar , Ratones , Animales , Humanos , Subtipo H1N1 del Virus de la Influenza A/genética , Aminoácidos/genética , Interacciones Microbiota-Huesped , Proteínas Virales/genética , Proteínas Virales/metabolismo , Hurones , Virus de la Influenza A/metabolismo , Aves , Nucleotidiltransferasas , Replicación Viral/genética , FilogeniaRESUMEN
Aurora kinase A (AURKA) performs critical functions in mitosis. Thus, the activity and subcellular localization of AURKA are tightly regulated and depend on diverse factors including interactions with the multiple binding cofactors. How these different cofactors regulate AURKA to elicit different levels of activity at distinct subcellular locations and times is poorly understood. Here, we identified a conserved region of CEP192, the major cofactor of AURKA, that mediates the interaction with AURKA. Quantitative binding studies were performed to map the interactions of a conserved helix (Helix-1) within CEP192. The crystal structure of Helix-1 bound to AURKA revealed a distinct binding site that is different from other cofactor proteins such as TPX2. Inhibiting the interaction between Helix-1 and AURKA in cells led to the mitotic defects, demonstrating the importance of the interaction. Collectively, we revealed a structural basis for the CEP192-mediated AURKA regulation at the centrosome, which is distinct from TPX2-mediated regulation on the spindle microtubule.
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Aurora Quinasa A , Huso Acromático , Aurora Quinasa A/genética , Aurora Quinasa A/metabolismo , Huso Acromático/metabolismo , Centrosoma/metabolismo , Microtúbulos/metabolismo , MitosisRESUMEN
Type â high Blaine ordinary Portland cement (IHB) possesses the same composition as that of type â ordinary Portland cement; however, due to its high fineness, IHB exhibits properties that are similar to those of type â ¢ rapid-hardening Portland cement, which can reduce the formwork striking time. However, to date, no quantitative research results regarding the construction-time-reduction effect of IHB have been reported. Therefore, this study conducted experiments to verify the formwork-striking-time reduction effect of concrete using IHB. Considering seasonal changes, the strength-development characteristics, according to the outside air temperature, were examined by modifying the curing temperature conditions (5, 10, and 20 °C). Furthermore, the achievable reduction in the concrete formwork striking time was quantitatively determined by comparing and analyzing with the linear interpolation and maturity methods for improving the accuracy of the formwork striking time. The experimental results indicated that, compared with ordinary cement, early formwork striking is possible using IHB, due to earlier strength development. Thus, IHB was confirmed to be effective for construction-time reduction through early formwork striking, and it can be used as a sufficient substitute for expensive rapid-hardening cement in sites and weather conditions where rapid hardening is required.
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Compared to the bottom ash obtained by a water-cooling system (wBA), dry process bottom ash (dBA) makes hardly any unburnt carbon because of its stay time at the bottom of the boiler and contains less chloride because there is no contact with seawater. Accordingly, to identify the chemical stability of dBA as a lightweight aggregate for construction purposes, the chemical properties of dBA were evaluated through the following process of the reviewing engineering properties of a lightweight aggregate (LWA). Typically, river gravel and crushed gravel have been used as coarse aggregates due to their physical and chemical stability. The coal ash and LWA, however, have a variety of chemical compositions, and they have specific chemical properties including SO3, unburnt coal and heavy metal content. As the minimum requirement to use the coal ash and lightweight aggregate with various chemical properties for concrete aggregate, the loss on ignition, the SO3 content and the amount of chloride should be examined, and it is also necessary to examine heavy metal leaching even though it is not included in the standard specifications in Korea. Based on the results, it is believed that there are no significant physical and chemical problems using dBA as a lightweight aggregate for concrete.
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Herein, we report a detailed study on the optoelectronic properties, photovoltaic performance, structural conformation, morphology variation, charge carrier mobility, and recombination dynamics in bulk heterojunction solar cells comprising a series of donor-acceptor conjugated polymers as electron donors based on benzodithiophene (BDT) and 5,8-bis(5-bromothiophen-2-yl)-6,7-difluoro-2,3-bis(3-(octyloxy)phenyl)quinoxaline as a function of the BDT's thienyl substitution (alkyl (WF3), alkylthio (WF3S), and fluoro (WF3F)). The synergistic positive effects of the fluorine substituents on the minimization of the bimolecular recombination losses, the reduction of the series resistances (RS), the increment of the shunt resistances (RSh), the suppression of the trap-assisted recombination losses, the balanced charge transport, the finer nanoscale morphology, and the deeper highest occupied molecular orbital (EHOMO) are manifested versus the alkyl and alkylthio substituents. According to these findings, the WF3F:[6,6]-phenyl-C71-butyric acid methyl ester (PC71BM)-based organic photovoltaic device is a rare example that features a high power conversion efficiency (PCE) of 17.34% under 500 lx indoor light-emitting diode light source with a high open-circuit voltage (VOC) of 0.69 V, due to the suppression of the voltage losses, and a PCE of 9.44% at 1 sun (100 mW/cm2) conditions, simultaneously.
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Monomeric perylene diimide (PDI) small molecules display a high absorption coefficient and crystallinity in solid-state thin films due to strong π-π interactions between the molecules. To take advantage of these exciting properties of PDIs, N,N'-bis(1-ethylpropyl)perylene-3,4,9,10-tetracarboxylic diimide (EP-PDI) was mixed with a binary blend of PTB7 and PC71 BM to fabricate an efficient ternary blend, which were in turn used to produce organic photovoltaic (OPV) devices well suited to indoor applications (PTB7=poly({4,8-bis[(2-ethylhexyl)oxy]benzo[1,2-b:4,5-b']dithiophene-2,6-diyl}{3-fluoro-2-[(2-ethylhexyl)carbonyl]thieno[3,4-b]thiophenediyl}), PC71 BM=[6,6]-phenyl-C71 -butyric acid methyl ester). We varied the PC71 BM/EP-PDI weight ratio to investigate the influence of EP-PDI on the optical, electrical, and morphological properties of the PTB7:PC71 BM:EP-PDI ternary blend. Compared with the reference PTB7:PC71 BM binary blend, the ternary blends showed strong optical absorption in the wavelength range in which the spectra of indoor LED lamps show their strongest peaks. The addition of EP-PDI to the binary blend was found to play an important role in altering the morphology of the blend in such a way as to facilitate charge transport in the resulting ternary blend. Apparently, as a result, the optimal PTB7:PC71 BM:EP-PDI-based inverted OPV device exhibited a power conversion efficiency (PCE) of 15.68 %, a fill factor (FF) of 68.5 %, and short-circuit current density (JSC ) of 56.7â µA cm-2 under 500â lx (ca. 0.17â mW cm-2 ) indoor LED light conditions.
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Resistive switching memory (ReRAM) has attracted much attention in recent times owing to its fast switching, simple structure, and non-volatility. Flexible and transparent electronic devices have also attracted considerable attention. We therefore fabricated an Al2O3-based ReRAM with transparent indium-zinc-oxide (IZO) electrodes on a flexible substrate. The device transmittance was found to be higher than 80% in the visible region (400-800 nm). Bended states (radius = 10 mm) of the device also did not affect the memory performance because of the flexibility of the two transparent IZO electrodes and the thin Al2O3 layer. The conduction mechanism of the resistive switching of our device was explained by ohmic conduction and a Poole-Frenkel emission model. The conduction mechanism was proved by oxygen vacancies in the Al2O3 layer, as analyzed by x-ray photoelectron spectroscopy analysis. These results encourage the application of ReRAM in flexible and transparent electronic devices.
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Zaltoprofen is a non-steroidal anti-inflammatory drug (NSAID) belonging to the propionic acid class. It has strong inhibitory effects on acute and chronic inflammation. Although zaltoprofen is well tolerated orally compared to other NSAIDs, it has to be administered in three to four doses per day and was associated with ulcerogenicity, bellyache and indigestion. This makes administration of zaltoprofen unsuitable for patients with gastric ulcer and is also associated with drug interactions. Therefore, it is important to develop an alternative dosage form which is easier to administer and avoids first-pass metabolism. The transdermal route meets all the above advantages. In this study, zaltoprofen gels were prepared using carbomer with mixture solution of polyethylene glycol (PEG) 400, Tween 80 and (2-hydroxypropyl)-ß-cyclodextrin (HPCD) (called as T2), subsequently oleic acid as a penetration enhancer was added. Zaltoprofen gel containing T2 and oleic acid could promote the percutaneous absorption of zaltoprofen and increase AUC by 183% compared to zaltoprofen gel without T2 and oleic acid. Also, there was a finding zaltoprofen gel containing T2 and oleic acid did not cause dermal irritations in an experimental animal.
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Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/química , Benzopiranos/administración & dosificación , Benzopiranos/química , Propionatos/administración & dosificación , Propionatos/química , 2-Hidroxipropil-beta-Ciclodextrina , Resinas Acrílicas/química , Administración Cutánea , Animales , Antiinflamatorios no Esteroideos/farmacocinética , Benzopiranos/farmacocinética , Línea Celular , Supervivencia Celular/efectos de los fármacos , Química Farmacéutica , Geles , Humanos , Masculino , Ratones , Ácido Oléico/química , Polietilenglicoles/química , Polisorbatos/química , Propionatos/farmacocinética , Ratas , Ratas Sprague-Dawley , Piel/efectos de los fármacos , Pruebas Cutáneas , Solubilidad , beta-Ciclodextrinas/químicaRESUMEN
New molecules having the structure of (E)-2-(4-tert-butylbenzylidene) hydrazinecarbothioamide (QNT3-18) or 4-tert-butylphenylthiourea (QNT3-20) was synthesized and presupposed to inhibit melanogenesis through the inhibition of tyrosinase, which is involved in melanin formation. Therefore, we seek to develop these new molecules as skin whitening agents in topical formulations based on preformulation studies. QNT3-18 or QNT3-20 showed a strong single endothermic peak at 159.34°C with 10.79 µm-sized or at 150.69°C with 9.0 µm-sized aggregated particles, respectively. Both QNT3-18 and QNT3-20 did not show cytotoxicity at effective concentration range (0.4 µM) against keratinocyte cells and QNT3-18 was more retained than QNT3-20 in the skin instead of permeating through the skin. QNT3-18 or QNT3-20 was practically insoluble in water; the aqueous solubility was 3.8 ± 0.37 or 130.6 ± 2.52 µg/mL, respectively. Also, the partition coefficient value (log P) corresponding to the quotient between aqueous and octanol concentration of the molecule was 3.9 or 2.6, respectively. The skin retention amount of QNT3-18 was 1.7-fold higher than that of QNT3-20. When the optimal SLN cream (J3 formulation) containing 4 µM QNT3-18 was applied on the backs of hairless rats for 4 days after UV irradiation for 7 days and the skin color was checked by reflectance spectrophotometer, the rat skin treated with SLN cream with QNT3-18 quickly recovered to normal compared to skin treated with SLN cream without QNT3-18. Taken together, this study suggests that topical formulations such as creams including SLNs with QNT3-18 might be appropriate carriers for skin whitening agents.
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Monofenol Monooxigenasa/antagonistas & inhibidores , Preparaciones para Aclaramiento de la Piel/química , Pigmentación de la Piel/efectos de los fármacos , Piel/efectos de los fármacos , Tiosemicarbazonas/química , Administración Cutánea , Animales , Descubrimiento de Drogas , Masculino , Ratas , Ratas sin Pelo , Preparaciones para Aclaramiento de la Piel/farmacología , Tiosemicarbazonas/farmacologíaRESUMEN
The objective of this study was to evaluate the potential of surface-modified paclitaxel (PTX)-incorporated solid lipid nanoparticles with hydroxypropyl-ß-cyclodextrin (smPSH). The smPSH released 89.70 ± 3.99% of its entrapped PTX within 24 h when placed in dissolution medium containing sodium lauryl sulfate. The cellular uptake of PTX from smPSH in Caco-2 cells was 5.3-fold increased compared to a PTX solution based on a Taxol formulation. Moreover, smPSH showed an increased cytotoxicity compared to PTX solution. In addition, AUC (5.43 µgâ¢h/ml) and Cmax (1.44 µg/ml) of smPSH were higher than those (1.81 µgâ¢h/ml and 0.73 µg/ml) of PTX solution. The drug concentration of smPSH (11.12 ± 4.45 ng/mg of lymph tissue) in lymph nodes was higher than that of the PTX solution (0.89 ± 0.75 ng/mg of lymph tissue), suggesting that more PTX was transported to the lymphatic vessels in the form of smPSH. In conclusion, smPSH have a potential as an alternative delivery system for oral administration of PTX.
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Antineoplásicos Fitogénicos/administración & dosificación , Portadores de Fármacos/química , Nanopartículas/química , Paclitaxel/administración & dosificación , beta-Ciclodextrinas/química , 2-Hidroxipropil-beta-Ciclodextrina , Administración Oral , Animales , Antineoplásicos Fitogénicos/farmacocinética , Antineoplásicos Fitogénicos/farmacología , Células CACO-2 , Supervivencia Celular/efectos de los fármacos , Humanos , Masculino , Neoplasias/tratamiento farmacológico , Paclitaxel/farmacocinética , Paclitaxel/farmacología , Ratas , Ratas Sprague-DawleyRESUMEN
Prilocaine, one of local anesthetics, has been used for regional pain relief. When applied as an ointments or creams, it is hard to expect their effects to last for long time, because they are easily removed by wetting, movement and contacting. For more comfortable and better application, we developed a prilocaine gel system using a bioadhesive polymer, carboxymethyl cellulose (CMC). For suitable bioadhesion, the bioadhesive force of various polymers was tested using an auto-peeling tester. The bioadhesive force of various types of CMC such as 100MC, 150MC and 300MC, was 0.0264, 0.0461 and 0.0824 N, at 1.5% concentration, respectively. The CMC-300MC gels showed the most suitable bioadhesive forces. The effect of drug concentration on drug release was studied from the prepared 1.5% CMC gels using a synthetic cellulose membrane at 37 ± 0.5°C. As the concentration of drug increased, the drug release increased. The effects of temperature on drug release from the 1.0% prilocaine gels were evaluated at 27, 32, 37 and 42°C. As the temperature of the drug gels increased, drug release increased. The enhancing effects of penetration enhancers such as pyrrolidones, non-ionic surfactants, fatty acids and propylene glycol derivatives were studied. Among the enhancers used, polyoxyethylene 2-oleyl ether was superior. The anesthetic effects were studied by a tail flick analgesic meter. In the rat tailflick test, 1.0% prilocaine gels containing polyoxyethylene 2-oleyl ether showed the most prolonged local analgesic effects. The results support the view that prilocaine gels with enhanced local anesthetic action could be developed using CMC bioadhesive polymer.
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Anestésicos Locales/farmacología , Carboximetilcelulosa de Sodio/química , Portadores de Fármacos , Umbral del Dolor/efectos de los fármacos , Prilocaína/farmacología , Adhesividad , Administración Cutánea , Administración Tópica , Anestésicos Locales/administración & dosificación , Anestésicos Locales/química , Anestésicos Locales/metabolismo , Animales , Química Farmacéutica , Excipientes/química , Excipientes/farmacología , Geles , Imidazoles/química , Cinética , Masculino , Polietilenglicoles/química , Polietilenglicoles/farmacología , Prilocaína/administración & dosificación , Prilocaína/química , Prilocaína/metabolismo , Ratas , Ratas Sprague-Dawley , Piel/metabolismo , Absorción Cutánea , Solubilidad , Tecnología Farmacéutica/métodos , Temperatura , ViscosidadRESUMEN
Gemcitabine microparticles were prepared using chitosan, polyethylene oxide or carbopol as the mucoadhesive polymer and eudragit L100-55 as the enteric polymer by a double emulsion method. The particle size and zeta potential changed from 1338.3 ± 254.1 nm to 2459.4 ± 103.6 nm and -5.16 ± 1.62 mV to 2.84 ± 0.65 mV, respectively, with increasing chitosan to gemcitabine weight ratio from 0.25 to 1. The gemcitabine-loaded microparticles without mucoadhesive polymer (F50) showed the particle size and zeta potential of 671.3 ± 58.3 nm and - 16.7 ± 1.82 mV, respectively. The cellular uptake of gemcitabine into Caco-2 cells from gemcitabine-loaded microparticles with chitosan increased with increasing incubation time in Caco-2 cells compared to that of gemcitabine-loaded microparticles with polyethylene oxide or carbopol, suggesting that chitosan might be the optimal mucoadhesive polymer. Gemcitabine microparticles will be tested to identify whether the oral absorption could be increased in the future.
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Antimetabolitos Antineoplásicos/administración & dosificación , Quitosano/química , Desoxicitidina/análogos & derivados , Portadores de Fármacos/química , Polietilenglicoles/química , Polivinilos/química , Resinas Acrílicas/química , Administración Oral , Antimetabolitos Antineoplásicos/farmacocinética , Células CACO-2 , Desoxicitidina/administración & dosificación , Desoxicitidina/farmacocinética , Humanos , Microesferas , Tamaño de la Partícula , GemcitabinaRESUMEN
BACKGROUND: Gemcitabine must be administered at high doses to elicit the required therapeutic response because of its very short plasma half-life due to rapid metabolism. These high doses can have severe adverse effects. METHODS: In this study, polymeric microparticulate systems of gemcitabine were prepared using chitosan as a mucoadhesive polymer and Eudragit L100-55 as an enteric copolymer. The physicochemical and biopharmaceutical properties of the resulting systems were then evaluated. RESULTS: There was no endothermic peak for gemcitabine in any of the polymeric gemcitabine microparticulate systems, suggesting that gemcitabine was bound to chitosan and Eudragit L100-55 and its crystallinity was changed into an amorphous form. The polymeric gemcitabine microparticulate system showed more than 80% release of gemcitabine in 30 minutes in simulated intestinal fluid. When mucin particles were incubated with gemcitabine polymeric microparticulates, the zeta potential of the mucin particles was increased to 1.57 mV, indicating that the polymeric gemcitabine microparticulates were attached to the mucin particles. Furthermore, the F53 polymeric gemcitabine microparticulates having 150 mg of chitosan showed a 3.8-fold increased uptake of gemcitabine into Caco-2 cells over 72 hours compared with gemcitabine solution alone. CONCLUSION: Overall, these results suggest that polymeric gemcitabine microparticulate systems could be used as carriers to help oral absorption of gemcitabine.
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Quitosano/química , Desoxicitidina/análogos & derivados , Portadores de Fármacos/química , Resinas Acrílicas/administración & dosificación , Resinas Acrílicas/química , Adsorción , Células CACO-2 , Rastreo Diferencial de Calorimetría , Supervivencia Celular/efectos de los fármacos , Quitosano/administración & dosificación , Desoxicitidina/administración & dosificación , Desoxicitidina/química , Desoxicitidina/farmacocinética , Desoxicitidina/toxicidad , Portadores de Fármacos/administración & dosificación , Humanos , Secreciones Intestinales , Modelos Biológicos , Mucinas/química , Nanomedicina , Propiedades de Superficie , GemcitabinaRESUMEN
Topical drug dosage forms such as ointments and creams can be easily removed through wetting, movement and contact. The new bioadhesive formulations with enhanced local anesthetic effects are needed for topical administration. The adhesive capacity of hydroxypropyl methylcellulose (HPMC) was determined by measuring the maximum detachment force and the adhesion work with an auto peeling tester. The release of drug from a HPMC gel was studied according to the drug concentration. Permeation study through the rat skin was performed at 37°C using phosphate buffer solution (pH = 7.4) as a receptor medium. To increase the skin permeation of bupivacaine from the HPMC gels, penetration enhancer such as the saturated and unsaturated fatty acids, the pyrrolidones, the propylene glycol derivatives, the glycerides, and the non-ionic surfactants were incorporated in the bupivacaine-HPMC gels. The local anesthetic effect of the formulated gel preparation was examined using a tail-flick analgesimeter. As the concentration of HPMC increased, the bioadhesive force and viscosity were increased. The rate of drug release was increased with increasing the drug concentration. Among the enhancers used, polyoxyethylene 2-oleyl ether showed the most enhancing effects on drug permeation through the skin. In the rat tail flick test, the area under the efficacy curve of bupivacaine gel containing polyoxyethylene 2-oleyl ether and tetrahydrozoline showed a 2.36-fold increase in anesthetic activity compared to control gel without any additives. The bupivacaine gels containing both penetration enhancer and vasoconstrictor showed enhancement and prolonged efficacy compared to the control gel. To enhance the local anesthetic effects of bupivacaine, the transdermal bupivacaine gel formulation containing penetration enhancer and vasoconstrictor could be developed.
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BACKGROUND: Nanoparticles fabricated from the biodegradable and biocompatible polymer, polylactic-co-glycolic acid (PLGA), are the most intensively investigated polymers for drug delivery systems. The objective of this study was to explore fully the development of a PLGA nanoparticle drug delivery system for alternative preparation of a commercial formulation. In our nanoparticle fabrication, our purpose was to compare various preparation parameters. METHODS: Docetaxel-loaded PLGA nanoparticles were prepared by a single emulsion technique and solvent evaporation. The nanoparticles were characterized by various techniques, including scanning electron microscopy for surface morphology, dynamic light scattering for size and zeta potential, x-ray photoelectron spectroscopy for surface chemistry, and high-performance liquid chromatography for in vitro drug release kinetics. To obtain a smaller particle, 0.2% polyvinyl alcohol, 0.03% D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), 2% Poloxamer 188, a five-minute sonication time, 130 W sonication power, evaporation with magnetic stirring, and centrifugation at 8000 rpm were selected. To increase encapsulation efficiency in the nanoparticles, certain factors were varied, ie, 2-5 minutes of sonication time, 70-130 W sonication power, and 5-25 mg drug loading. RESULTS: A five-minute sonication time, 130 W sonication power, and a 10 mg drug loading amount were selected. Under these conditions, the nanoparticles reached over 90% encapsulation efficiency. Release kinetics showed that 20.83%, 40.07%, and 51.5% of the docetaxel was released in 28 days from nanoparticles containing Poloxamer 188, TPGS, or polyvinyl alcohol, respectively. TPGS and Poloxamer 188 had slower release kinetics than polyvinyl alcohol. It was predicted that there was residual drug remaining on the surface from x-ray photoelectron spectroscopy. CONCLUSION: Our research shows that the choice of surfactant is important for controlled release of docetaxel.
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Ácido Láctico/química , Nanopartículas/química , Ácido Poliglicólico/química , Taxoides/química , Acetatos , Centrifugación , Cloroformo , Docetaxel , Nanocápsulas/química , Tamaño de la Partícula , Espectroscopía de Fotoelectrones , Poloxámero , Polietilenglicoles , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Alcohol Polivinílico , Sonicación , Tensión Superficial , Tensoactivos , Vitamina E/análogos & derivadosRESUMEN
The larvicidal activity of 11 Myrtaceae essential oils and their constituents was evaluated against Aedes aegypti L. Of the 11, Melaleuca linariifolia Sm., Melaleuca dissitiflora F. Muell., Melaleuca quinquenervia (Cav.) S. T. Blake, and Eucalyptus globulus Labill oils at 0.1 mg/ml exhibited > or = 80% larval mortality. At this same concentration, the individual constituents tested, allyl isothiocyanate, alpha-terpinene, p-cymene, (+)-limonene, (-)-limonene, gamma-terpinene, and (E)-nerolidol, resulted in > or = 95% mortality. We also tested the acute toxicity of these four active oils earlier mentioned and their constituents against Daphnia magna Straus. M. linariifolia and allyl isothiocyanate was the most toxic to D. magna. Twodays after treatment, residues of M. dissitiflora, M. linariifolia, M. quinquenervia, and E. globulus oils in water were 55.4, 46.6, 32.4, and 14.8%, respectively. Less than 10% of allyl isothiocyanate, alpha-terpinene, p-cymene, (-)-limonene, (+)-limonene, and gamma-terpinene was detected in the water at 2 d after treatment. Our results indicated that oils and their constituents could easily volatilize in water within a few days after application, thus minimizing their effect on the aqueous ecosystem. Therefore, Myrtaceae essential oils and their constituents could be developed as control agents against mosquito larvae.
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Aedes/efectos de los fármacos , Daphnia/efectos de los fármacos , Myrtaceae/química , Aceites Volátiles/farmacología , Aceites de Plantas/farmacología , Animales , Insecticidas/química , Insecticidas/farmacología , Larva/efectos de los fármacos , Aceites Volátiles/química , Residuos de Plaguicidas , Aceites de Plantas/química , Pruebas de Toxicidad , Agua , Contaminantes Químicos del AguaRESUMEN
The purpose of this study was to investigate the effect of oral myricetin on the bioavailability and pharmacokinetics of orally and intravenously administered doxorubicin (DOX) in rats for oral delivery. The effect of myricetin on the P-glycoprotein (P-gp) and CYP3A4 activity was also evaluated. Myricetin inhibited CYP3A4 enzyme activity with 50% inhibition concentration of 7.8 µM. In addition, myricetin significantly enhanced the cellular accumulation of rhodamine 123 in MCF-7/ADR cells overexpressing P-gp. The pharmacokinetic parameters of DOX were determined in rats after oral (40 mg/kg) or intravenous (10 mg/kg) administration of DOX to rats in the presence and absence of myricetin (0.4, 2 or 10 mg/kg). Compared to the control group, myricetin significantly (p < 0.05, 2 mg/kg; p < 0.01, 10 mg/kg) increased the area under the plasma concentration-time curve (AUC, 51-117% greater) of oral DOX. Myricetin also significantly (p < 0.05, 2 mg/kg; p < 0.01, 10 mg/kg) increased the peak plasma concentration of DOX. Consequently, the absolute bioavailability of DOX was increased by myricetin compared to that in the control group, and the relative bioavailability of oral DOX was increased by 1.51- to 2.17-fold. The intravenous pharmacokinetics of DOX were not affected by the concurrent use of myricetin in contrast to the oral administration of DOX. Accordingly, the enhanced oral bioavailability in the presence of myricetin, while there was no significant change in the intravenous pharmacokinetics of DOX, could be mainly due to the increased intestinal absorption via P-gp inhibition by myricetin rather than to the reduced elimination of DOX. These results suggest that the increase in the oral bioavailability of DOX might be mainly attributed to enhanced absorption in the gastrointestinal tract via the inhibition of P-gp and to reduced first-pass metabolism of DOX due to inhibition of CYP3A in the small intestine and/or in the liver by myricetin.
Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/antagonistas & inhibidores , Antibióticos Antineoplásicos/farmacocinética , Inhibidores del Citocromo P-450 CYP3A , Citocromo P-450 CYP3A/metabolismo , Doxorrubicina/farmacocinética , Flavonoides/administración & dosificación , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Administración Oral , Animales , Disponibilidad Biológica , Doxorrubicina/sangre , Interacciones Farmacológicas , Flavonoides/farmacología , Inyecciones Intravenosas , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
This study examined a novel alendronate formulation that was developed to overcome the shortcomings of alendronate, such as its low bioavailability and gastric adverse effects. Alendronate microparticles were prepared using mucoadhesive polymers such as chitosan for improving the intestinal cellular absorption of alendronate and also using a gastric-resistant polymer such as Eudragit L100-55 for reducing the gastric inflammation of alendronate. Alendronate microparticles including chitosan showed a threefold increase in alendronate uptake (6.92 ± 0.27%) in Caco-2 cells when compared with the uptake of alendronate solution (2.38 ± 0.27%) into Caco-2 cells. Most interestingly, alendronate microparticles including chitosan showed 2.80 x 10â»6 cm/s of an apparent permeability coefficient across Caco-2 cells and caused a significant 42.4% enhancement compared with that of alendronate solution across Caco-2 cells. The morphology of the Caco-2 cells treated with alendronate microparticles including chitosan was similar to that of the untreated cells and alendronate microparticles exhibited a negative effect to propodium iodide with some annexin-V fluorescence isothiocyante positive effect. It was proposed that the novel alendronate microparticles could possess the potential of an increased intestinal absorption and fewer adverse effects of alendronate.