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1.
Cell Mol Biol (Noisy-le-grand) ; 67(1): 64-72, 2021 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-34817366

RESUMEN

The purpose of our study was to obtain new wound dressings in the form of hydrogels that promote wound healing taking advantage of the broad activities of elastin (ELT) in physiological processes. The hydrogel of ELT and polyvinylpyrrolidone (PVP; ELT-PVP) was obtained by cross-linking induced by gamma irradiation at a dose of 25 kGy. The physicochemical changes attributed to cross-linking were analyzed through scanning electron microscopy (SEM), infrared spectroscopy analysis with Fourier transform (FTIR), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). Furthermore, we performed a rheological study to determine the possible changes in the fluidic macroscopic properties produced by the cross-linking method. Finally, we accomplished viability and proliferation analyses of human dermal fibroblasts in the presence of the hydrogel to evaluate its biological characteristics. The hydrogel exhibited a porous morphology, showing interconnected porous with an average pore size of 16 ± 8.42 µm. The analysis of FTIR, DSC, and TGA revealed changes in the chemical structure of the ELT-PVP hydrogel after the irradiation process. Also, the hydrogel exhibited a rheological behavior of a pseudoplastic and thixotropic fluid. The hydrogel was biocompatible, demonstrating high cell viability, whereas ELT presented low biocompatibility at high concentrations. In summary, the hydrogel obtained by gamma irradiation revealed the appropriate morphology to be applied as a wound dressing. Interestingly, the hydrogel exhibited a higher percentage of cell viability compared with ELT, suggesting that the cross-linking of ELT with PVP is a suitable strategy for biological applications of ELT without generating cellular damage.


Asunto(s)
Materiales Biocompatibles/metabolismo , Elastina/metabolismo , Apósitos Oclusivos , Polimerizacion/efectos de la radiación , Povidona/metabolismo , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Rastreo Diferencial de Calorimetría/métodos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Elastina/química , Elastina/ultraestructura , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Humanos , Hidrogeles/química , Hidrogeles/metabolismo , Hidrogeles/farmacología , Microscopía Electrónica de Rastreo , Povidona/química , Povidona/farmacología , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Termogravimetría/métodos , Cicatrización de Heridas/efectos de los fármacos
2.
ACS Appl Mater Interfaces ; 12(41): 45859-45872, 2020 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-32967419

RESUMEN

Bacteria responsive color-changing wound dressings offer a valuable platform for continuous monitoring of the wound bed facilitating early detection of bacterial infections. In this study, we present a highly sensitive electrospun nanofibrous polyurethane wound dressing incorporating a hemicyanine-based chromogenic probe with a labile ester linkage that can be enzymatically cleaved by bacterial lipase released from clinically relevant strains, such as Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA). A rapid chromogenic response was achieved by localizing the dye at the surface of core-shell fibers, resulting in a 5x faster response relative to conventional nanofibers. By incorporating polyvinylpyrrolidone (PVP) dopant in the shell, the sensitivity was boosted to enable detection of bacteria at clinically relevant concentrations after 2 h exposure: 2.5 × 105 CFU/cm2 P. aeruginosa and 1.0 × 106 CFU/cm2 MRSA. Introduction of PVP in the shell also boosted the degree of hydrolysis of the chromogenic probe by a factor of 1.2× after a 3 h exposure to a low concentration of P. aeruginosa (105 CFU/cm2). PVP was also found to improve the discernibility of the color change at high bacterial concentrations. The co-operativity between the chromogenic probe, fiber structure, and polymer composition is well-suited for timely in situ detection of wound infection.


Asunto(s)
Infecciones Bacterianas/diagnóstico , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Nanofibras/química , Poliuretanos/química , Povidona/química , Pseudomonas aeruginosa/aislamiento & purificación , Colorimetría , Lipasa/metabolismo , Staphylococcus aureus Resistente a Meticilina/enzimología , Estructura Molecular , Tamaño de la Partícula , Poliuretanos/metabolismo , Povidona/metabolismo , Pseudomonas aeruginosa/enzimología , Propiedades de Superficie
3.
Hum Cell ; 33(4): 1294-1301, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32710259

RESUMEN

Carcinostatic effects of combined use of hydrogen nano-bubbles (nano-H) and platinum-povidone (PVP--Pt) were examined. Hydrogen-dissolved medium was prepared by hydrogen-gas bubbling with a microporous gas-emittance-terminal into a medium in the absence or presence of PVP-Pt (nano-H, nano-H/PVP-Pt). Human esophagus-derived carcinoma cells KYSE70 were repressed for cell proliferation with nano-H/PVP-Pt more markedly than with nano-H, indicating the hydrogen-intensification for PVP-Pt-alone-carcinostasis. However, the intensified carcinostasis required co-administration of nano-H and PVP-Pt, and no intensified carcinostasis was shown in two-step separate administration of nano-H and PVP-Pt. Furthermore, hydrogen bubbling into PVP-Pt-containing medium achieved more appreciable carcinostasis than mere addition of PVP-Pt into nano-H-containing medium, indicating the potent interaction of hydrogen and PVP-Pt. The nano-H/PVP-Pt-administered human tongue-derived carcinoma cells HSC-4 were repressed for cell proliferation more markedly than pre-malignant human tongue-derived epitheliocytes DOK, concurrently with more abundant intracellular Pt-intake into HSC-4 cells than DOK as analyzed by ICP-MS. Thus, PVP-Pt is able to adsorb hydrogen nano-bubbles on Pt and applicable for cancer therapy by diminishing the side-effects to normal cells.


Asunto(s)
Antineoplásicos , Carcinoma/patología , Proliferación Celular/efectos de los fármacos , Interacciones Farmacológicas , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patología , Hidrógeno/farmacología , Nanopartículas , Compuestos de Platino/efectos adversos , Compuestos de Platino/metabolismo , Compuestos de Platino/farmacología , Povidona/efectos adversos , Povidona/farmacología , Neoplasias de la Lengua/metabolismo , Neoplasias de la Lengua/patología , Carcinoma/metabolismo , Línea Celular Tumoral , Coloides , Medios de Cultivo , Combinación de Medicamentos , Neoplasias Esofágicas/tratamiento farmacológico , Gases , Humanos , Hidrógeno/administración & dosificación , Povidona/metabolismo , Neoplasias de la Lengua/tratamiento farmacológico
4.
J Mater Chem B ; 8(27): 5921-5927, 2020 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-32542300

RESUMEN

Hydrogel-based multifunctional materials have attracted much attention. In this work, novel mineralized hydrogels were fabricated through physically cross-linked polyvinylpyrrolidone (PVP) and CaCO3. The mineralized hydrogels were prepared by simply mixing CaCl2, Na2CO3, and PVP in aqueous solutions. The CO32- induced the aggregation of the PVP chains and the CaCO3 particles in situ generated in the aqueous solution worked as fillers to strengthen the hydrogels. Based on this method, other kinds of mineralized hydrogels were prepared by replacing the Ca2+ with different metal ions. The mineralized hydrogels displayed shapeable, self-healing and thixotropic properties. Moreover, the mineralized hydrogel-based sensor showed good and stable sensitivity to compressive pressure, and could be used to monitor human actions. This work presents a facile method for preparing mineralized hydrogels, which are promising for various applications due to their outstanding properties.


Asunto(s)
Hidrogeles/química , Minerales/química , Povidona/química , Cicatrización de Heridas/efectos de los fármacos , Carbonato de Calcio/química , Cloruro de Calcio/química , Carbonatos/química , Cationes Bivalentes/química , Vendajes de Compresión , Fuerza Compresiva , Reactivos de Enlaces Cruzados/química , Humanos , Hidrogeles/metabolismo , Povidona/metabolismo , Reología
5.
Talanta ; 216: 120960, 2020 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-32456941

RESUMEN

A novel ferricyanide/Prussian blue (PB) assay for total antioxidant capacity (TAC) determination was developed exploiting the formation of PB nanoparticles in the presence of polyvinylpyrrolidone (PVP) as stabilizer. This improved method, named as "nanoparticle-based ferricyanide/Prussian blue assay (PBNP)", was applied to the TAC measurement of Cynara Scolymus L. (globe artichoke). The calibration results of the novel (PBNP) method were compared with those of a similar nanoparticle PB method performed in the absence of PVP, and of a sodium dodecyl sulfate-modified and acid-optimized ferricyanide reference assay. Compared to similar common Fe(III)-based TAC assays, much higher molar absorptivities, pointing out higher response to different kinds of antioxidants, were obtained with PBNP for all tested antioxidants, and lower LOD and LOQ values were achieved for thiols. As an additional advantage, methionine, not responding to other electron-transfer based TAC reagents, could be measured. PBNP could detect various antioxidants with one-two orders-of-magnitude lower LOD values than those of widely used TAC assays like CUPRAC and Folin-Ciocalteau well correlating with the proposed assay.


Asunto(s)
Antioxidantes/metabolismo , Cynara scolymus/metabolismo , Ferricianuros/química , Ferrocianuros/química , Nanopartículas/química , Antioxidantes/análisis , Calibración , Cynara scolymus/química , Povidona/química , Povidona/metabolismo
6.
J Appl Toxicol ; 40(6): 815-831, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-31984544

RESUMEN

This study evaluated the biodistribution and organ oxidative effects of silver nanoparticles (AgNPs) coated with/without polyvinylpyrrolidone (PVP) (AgNP-20 and AgNP-PVP) in mice; these were administered by gavage at a dose of 10-250 mg/kg body weight per day for 28 days. The results showed that both the AgNPs could induce subacute toxicity and oxidative damage to mice and were mainly accumulated in the liver and spleen and excreted by feces. AgNPs could be absorbed into blood and might cross the blood-brain barrier, and be distributed extensively in mice. The malondialdehyde content in the liver, lungs and kidneys increased in both AgNP groups, while the content of glutathione decreased, and the activity of superoxide dismutase increased at first and then decreased along with the increased doses. Inflammatory pathological changes in the lung and liver at high dose of both AgNPs were consistent with increases in glutamate pyruvic transaminase, glutamate oxaloacetic transaminase and the total protein in serum detection. The Ag content was detected in organs, with the highest content in the liver, followed by spleen, while the Ag content in feces was about 500 times higher than that in urine. AgNP-PVP could induce higher oxidative stress and subacute toxicity than AgNP-20 at the same dose, which might be related to the higher concentrations and more Ag+ ions released in mice after AgNP-PVP exposure. The data from this research provided information on toxicity and biodistribution of AgNPs following gavage administration in mice, and might shed light for future application of AgNPs in daily life.


Asunto(s)
Nanopartículas del Metal/toxicidad , Povidona/toxicidad , Compuestos de Plata/toxicidad , Administración Oral , Animales , Femenino , Masculino , Nanopartículas del Metal/administración & dosificación , Ratones Endogámicos ICR , Povidona/metabolismo , Compuestos de Plata/administración & dosificación , Compuestos de Plata/metabolismo , Distribución Tisular
7.
Platelets ; 31(2): 258-264, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31057000

RESUMEN

The isolation of mitochondria is gaining importance in experimental and clinical laboratory settings. The mitochondrion is known as the powerhouse of the cell as it produces the energy to power most cellular functions but is also involved in many cellular processes. Of interest, mitochondria and mitochondrial components (i.e. circular DNA, N-formylated peptides, cardiolipin) have been involved in several human inflammatory pathologies, such as cancer, Alzheimer's disease, Parkinson's disease, and rheumatoid arthritis. Therefore, stringent methods of isolation and purification of mitochondria are of the utmost importance in assessing mitochondrial-related diseases. While several mitochondrial isolation methods have been previously published, these techniques are aimed at yielding mitochondria from cells types other than platelets. In addition, little information is known on the number of platelet-derived microparticles that can contaminate the mitochondrial preparation or even the overall quality and integrity of the mitochondria. In this project, we provide an alternate purification method yielding mitochondria of high purity and integrity from human platelets. Using human platelets, flow cytometry and transmission electron microscopy experiments were performed to demonstrate that the Percoll gradient method yielded significantly purified mitochondria by removing platelet membrane debris. Mitochondrial respiration following the substrate-uncoupler-inhibitor-titration (SUIT) protocol was similar in both the purified and crude mitochondrial extraction methods. Finally, the cytochrome c effect and JC-1 staining did not exhibit a significant difference between the two methods, suggesting that the mitochondrial integrity was not affected. Our study suggests that the Percoll discontinuous gradient purifies viable platelet-derived mitochondria by removing platelet-derived debris, including microparticles, therefore confirming that this isolation method is ideal for studying the downstream effects of intact mitochondria in mitochondrial-related diseases.


Asunto(s)
Mitocondrias/metabolismo , Povidona/metabolismo , Dióxido de Silicio/metabolismo , Humanos
10.
AAPS PharmSciTech ; 20(1): 37, 2019 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-30604142

RESUMEN

The purpose of this study was to research a novel combination of Plasdone-S630 and HPMCAS-HF as hot-melt carrier used in ziprasidone hydrochloride for enhanced oral bioavailability and dismissed food effect. Ziprasidone hydrochloride solid dispersion (ZH-SD) was prepared by hot-melt extrusion technique, and its optimized formulation was selected by the central composite design (CCD), which was characterized for powder X-ray diffraction (PXRD), fourier transform infrared spectroscopy (FTIR), in vitro dissolution study, and stability study. Finally, the in vivo study in fasted/fed state was carried out in beagle dogs. Based on PXRD analysis, HME technique successfully dispersed ziprasidone with a low crystallinity hydrochloride form in the polymers. According to the analysis of FTIR, hydrogen bonds were formed between drug and polymers during the process of HME. Without any noticeable bulk, crystalline could be found from the micrograph of ZH-SD when analyzed the result of scanning electron microscope (SEM). Pharmacokinetics studies indicated that the bioavailability of ZH-SD formulation had no significant difference in fasted and fed state, and the Cmax and AUC of ZH-SD were two fold higher than Zeldox® in fasted state. This result indicated that ziprasidone has achieved a desired oral bioavailability in fasted state and no food effect.


Asunto(s)
Ayuno , Metilcelulosa/análogos & derivados , Piperazinas/síntesis química , Povidona/síntesis química , Tiazoles/síntesis química , Administración Oral , Animales , Disponibilidad Biológica , Perros , Combinación de Medicamentos , Ayuno/metabolismo , Metilcelulosa/administración & dosificación , Metilcelulosa/síntesis química , Metilcelulosa/metabolismo , Excipientes Farmacéuticos/administración & dosificación , Excipientes Farmacéuticos/metabolismo , Piperazinas/administración & dosificación , Piperazinas/farmacocinética , Povidona/administración & dosificación , Povidona/metabolismo , Solubilidad , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Tiazoles/administración & dosificación , Tiazoles/farmacocinética , Difracción de Rayos X/métodos
11.
Eur J Pharm Sci ; 114: 84-92, 2018 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-29203152

RESUMEN

In-vitro permeation studies were conducted to assess the feasibility of fabricating dissolving-microneedle-array systems to release sumatriptan succinate. The formulations consisted mainly of the encapsulated active ingredient and a water-soluble biologically compatible polymer, polyvinylpyrrolidone (PVP), approved by the U.S. Food and Drug Administration (FDA). Tests with Franz-type diffusion cells and Göttingen minipig skins showed an increase of the transdermal flux compared to passive diffusion. A preparation, containing 30% by mass of PVP and 8.7mg sumatriptan, produced a delivery rate of 395±31µg/cm2h over a 7-hour period after a negligible lag time of approximately 39min. Theoretically, a 10.7cm2 microneedle-array patch loaded with 118.8mg of the drug would provide the required plasma concentration, 72ng/mL, for nearly 7h.


Asunto(s)
Sistemas de Liberación de Medicamentos/métodos , Microinyecciones/métodos , Povidona/metabolismo , Absorción Cutánea/fisiología , Sumatriptán/metabolismo , Animales , Femenino , Técnicas de Cultivo de Órganos , Excipientes Farmacéuticos/administración & dosificación , Excipientes Farmacéuticos/metabolismo , Povidona/administración & dosificación , Absorción Cutánea/efectos de los fármacos , Solubilidad , Sumatriptán/administración & dosificación , Porcinos , Porcinos Enanos , Vasoconstrictores/administración & dosificación , Vasoconstrictores/metabolismo
12.
Biomed Pharmacother ; 92: 479-490, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28570982

RESUMEN

In the recent years, synthesis of nanomaterials using seaweeds and their diverse applications is escalating research in modern era. Among the noble metals, platinum nanoparticles (PtNPs) are of great importance owing to their catalytic property and less toxicity. The significance of this work is a simple one-step synthesis of PtNPs using aqueous extract of Indian brown seaweed Padina gymnospora and their catalytic activity with a polymer Polyvinylpyrrolidone (PVP) as PVP/PtNPs nanocomposite towards antimicrobial, haemolytic, cytotoxic (Artemia salina) and antioxidant properties. Fourier Transform Infrared (FT-IR) spectrum results showed diversified functional groups (biomoeities such as carbohydrates and proteins) present in the seaweed extract is responsible for the reduction of platinum ions (Pt+) to PtNPs. The seaweed mediated PtNPs was characterized by UV-vis spectrophotometer, X-ray diffraction (XRD) pattern, Field Emission Scanning Electron Microscopy (FESEM) equipped with Energy Dispersive X-ray (EDX) spectroscopy and High Resolution Transmission Electron Microscopy (HRTEM) analysis. The synthesized PtNPs was found to be truncated octahedral in shape with the range of 5-50nm. Crystalline nature of the nanoparticles was evidenced by Selected Area Electron Diffraction (SAED) pattern with bright circular spots corresponding to (111), (200), (220) and (311) Bragg's reflection planes. The size of the PtNPs was further evidenced by Dynamic Light Scattering (DLS) analysis and it is originate to be stable at -22.5mV through Zeta Potential (ZP) analysis. The present study shows that the catalytic behavior of PtNPs as polymer/metal nanocomposite (PVP/PtNPs) preparation for an antibacterial activity against seven disease causing pathogenic bacterial strains with the maximum activity against Escherichia coli (15.6mm) followed by Lactococcus lactis (14.8mm) and Klebsiella pneumoniae (14.4mm). But no haemolytic activity was seen at their effective bactericidal concentration, whereas increase in the haeomyltic activity was seen only in higher concentrations (600, 900 and 1200µgmL-1). On the other hand, PVP/PtNPs nanocomposite has shown cytotoxic activity at 100±4µgmL-1 (LC50) against Artemia salina nauplii. Furthermore, PVP/PtNPs nanocomposite showed an enhanced scavenging activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH), superoxide, nitric oxide and hydroxyl radicals.


Asunto(s)
Tecnología Química Verde/métodos , Nanopartículas del Metal/química , Nanocompuestos/química , Platino (Metal)/química , Povidona/síntesis química , Algas Marinas , Animales , Antibacterianos/síntesis química , Antibacterianos/metabolismo , Antibacterianos/farmacología , Catálisis/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Hemólisis/efectos de los fármacos , Hemólisis/fisiología , Humanos , Nanopartículas del Metal/administración & dosificación , Pruebas de Sensibilidad Microbiana/métodos , Nanocompuestos/administración & dosificación , Phaeophyceae , Platino (Metal)/metabolismo , Platino (Metal)/farmacología , Povidona/metabolismo , Povidona/farmacología , Algas Marinas/metabolismo
13.
J Control Release ; 249: 11-22, 2017 03 10.
Artículo en Inglés | MEDLINE | ID: mdl-28109773

RESUMEN

Sustained pulmonary drug delivery is regarded as an effective strategy for local treatment of chronic lung diseases. Despite of the progress made so far, there remains a need for respirable drug loaded porous microparticles, where porosity of the microparticles can be readily engineered during the preparation process, with tunable sustained drug release upon lung deposition. In this work, polyvinyl pyrrolidone (PVP) was used as a novel porogen to engineer PLGA-based large porous particles (LPPs) using single emulsion method, with fine tuning of the porosity, sustained drug release both in vitro and in vivo. Using cinaciguat as the model drug, influence of PVP content and PLGA type on the properties of the LPPs was characterized, including geometric particle size, drug encapsulation efficiency, tap density, theoretical and experimental aerodynamic particle size, specific surface area, morphology, and in vitro drug release. Solid state of cinaciguat in the LPPs was studied based on DSC and X-ray analysis. LPPs retention in the rat lung was carried out using bronchoalveolar lavage fluid method. Raw 264.7 macrophage cells were used for LPPs uptake study. Pharmacodynamic study was performed in mini-pigs in a well-established model of pulmonary arterial hypertension (thromboxane challenge). It was demonstrated that porosity of the LPPs is tunable via porogen content variation. Cinaciguat can be released from the LPP in a controlled manner for over 168h. Significant reduction of macrophage phagocytosis was presented for LPPs. Furthermore, LPPs was found to have extended retention time (~36h) in the rat lung and accordingly, sustained pharmacodynamics effect was achieved in mini-pig model. Taken together, our results demonstrated that this simple PLGA based LPPs engineering using single emulsion method with PVP as porogen may find extensive application for the pulmonary delivery of hydrophobic drugs to realize tunable sustained effect with good safety profile.


Asunto(s)
Benzoatos/administración & dosificación , Preparaciones de Acción Retardada/química , Emulsiones/química , Ácido Láctico/química , Pulmón/metabolismo , Ácido Poliglicólico/química , Povidona/química , Animales , Benzoatos/farmacocinética , Preparaciones de Acción Retardada/metabolismo , Emulsiones/metabolismo , Ácido Láctico/metabolismo , Masculino , Ratones , Tamaño de la Partícula , Ácido Poliglicólico/metabolismo , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Porosidad , Povidona/metabolismo , Células RAW 264.7 , Ratas Sprague-Dawley
14.
Food Chem ; 214: 47-52, 2017 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-27507446

RESUMEN

Ochratoxin A (OTA) is a fungal metabolite and putative carcinogen which can contaminate a variety of foods such as cereals, wine, and nuts. Commercial ELISA kits are known to give false-positive results for OTA concentrations when phenolic compounds are present. Pistachios represent a food matrix rich in phenolic compounds potentially contaminated with OTA, and were used to model OTA cross-reactivity. Polyvinylpolypyrrolidone (PVPP) was incorporated during extraction of OTA using a commercial ELISA protocol. HPLC methods were used to confirm that PVPP does not interact with OTA and levels of gallic acid and catechin remaining in pistachio extracts decreased with increasing PVPP application. Cross-reactivity of extracts also decreased with increasing PVPP application, and color loss was used as an indicator of anthocyanin removal. Incorporating PVPP into ELISA protocols allows for the continued use of rapid immunological methods in food matrices containing phenolic compounds.


Asunto(s)
Ocratoxinas/análisis , Fenoles/análisis , Pistacia , Extractos Vegetales/análisis , Povidona/análogos & derivados , Anticuerpos/análisis , Anticuerpos/metabolismo , Catequina/análisis , Catequina/metabolismo , Cromatografía Líquida de Alta Presión/métodos , Reacciones Cruzadas/efectos de los fármacos , Grano Comestible/química , Ensayo de Inmunoadsorción Enzimática/métodos , Ocratoxinas/metabolismo , Fenoles/metabolismo , Extractos Vegetales/metabolismo , Povidona/metabolismo , Povidona/farmacología
15.
J Pharm Sci ; 106(3): 817-825, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-27923491

RESUMEN

The preparation of liquisolid systems presents a promising and innovative possibility for enhancing dissolution profiles and improving the bioavailability of poorly soluble drugs. This study aims to evaluate the differences in the properties of liquisolid systems containing combinations of 3 commercially used superdisintegrants (sodium starch glycolate, crospovidone, and croscarmellose sodium). Multiple regression models and contour plots were used to study how the amount and the type of superdisintegrant used affected the quality parameters of liquisolid tablets. The results revealed that an increased amount of crospovidone in the mixture improves disintegration and wetting time and enhances drug release from the prepared liquisolid tablets. Moreover, it was observed that a binary blend of crospovidone and sodium starch glycolate improved tablet disintegration. Considering the obtained results, it could be stated that crospovidone showed the best properties to be used as superdisintegrant for the preparation of liquisolid systems containing rosuvastatin.


Asunto(s)
Carboximetilcelulosa de Sodio/síntesis química , Química Farmacéutica/métodos , Povidona/síntesis química , Almidón/análogos & derivados , Carboximetilcelulosa de Sodio/farmacocinética , Formas de Dosificación , Liberación de Fármacos , Excipientes/síntesis química , Excipientes/farmacocinética , Excipientes Farmacéuticos/síntesis química , Excipientes Farmacéuticos/farmacocinética , Povidona/metabolismo , Proyectos de Investigación , Solubilidad , Almidón/síntesis química , Almidón/farmacocinética
16.
Int J Pharm ; 511(2): 983-93, 2016 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-27506511

RESUMEN

The saturation solubility of PVP:PZQ physical mixtures (PMs) and solid dispersions (SDs) prepared from ethanol (E/E) or ethanol/water (E/W) by the solvent evaporation method at 1:1, 2:1 and 3:1 ratio (w/w) was determined. The presence of PVP improves the solubility of PZQ (0.31±0.01mg/mL). A maximum of 1.29±0.03mg/mL of PZQ in solution was achieved for the 3:1 SD (E/E). The amount of PZQ in solution depends on the amount of polymer and on the preparation method. Solid-state NMR (ssNMR) and DSC were used to understand this behavior. Results show that PMs are a mixture of crystalline PZQ with the polymer, while SDs show different degrees of drug amorphization depending on the solvent used. For E/W SDs, PZQ exists in amorphous and crystalline states, with no clear correlation between the amount of crystalline PZQ and the amount of PVP. For E/E SDs, formulations with a higher percentage of PZQ are amorphous with the components miscible in domains larger than 3nm ((1)H ssNMR relaxation measurements). Albeit its higher saturation solubility, the 3:1 E/E PVP:PZQ sample has a significant crystalline content, probably due to the water introduced by the polymer. High PVP content and small crystal size account for this result.


Asunto(s)
Antihelmínticos/química , Povidona/química , Praziquantel/química , Solventes/química , Antihelmínticos/metabolismo , Rastreo Diferencial de Calorimetría/métodos , Cristalización , Composición de Medicamentos , Espectroscopía de Resonancia Magnética/métodos , Povidona/metabolismo , Praziquantel/metabolismo , Solubilidad , Solventes/metabolismo
17.
J Control Release ; 226: 238-47, 2016 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-26883753

RESUMEN

Microneedle technology provides the opportunity for the delivery of DNA therapeutics by a non-invasive, patient acceptable route. To deliver DNA successfully requires consideration of both extra and intracellular biological barriers. In this study we present a novel two tier platform; i) a peptide delivery system, termed RALA, that is able to wrap the DNA into nanoparticles, protect the DNA from degradation, enter cells, disrupt endosomes and deliver the DNA to the nucleus of cells ii) a microneedle (MN) patch that will house the nanoparticles within the polymer matrix, breach the skin's stratum corneum barrier and dissolve upon contact with skin interstitial fluid thus releasing the nanoparticles into the skin. Our data demonstrates that the RALA is essential for preventing DNA degradation within the poly(vinylpyrrolidone) (PVP) polymer matrix. In fact the RALA/DNA nanoparticles (NPs) retained functionality when in the MN arrays after 28days and over a range of temperatures. Furthermore the physical strength and structure of the MNs was not compromised when loaded with the NPs. Finally we demonstrated the effectiveness of our MN-NP platform in vitro and in vivo, with systemic gene expression in highly vascularised regions. Taken together this 'smart-system' technology could be applied to a wide range of genetic therapies.


Asunto(s)
Péptidos de Penetración Celular/química , ADN/administración & dosificación , Técnicas de Transferencia de Gen/instrumentación , Nanopartículas/química , Agujas , Plásmidos/administración & dosificación , Administración Cutánea , Animales , Línea Celular , Péptidos de Penetración Celular/metabolismo , ADN/química , ADN/genética , ADN/metabolismo , Femenino , Expresión Génica , Humanos , Ratones Endogámicos C57BL , Nanopartículas/metabolismo , Plásmidos/química , Plásmidos/genética , Plásmidos/metabolismo , Povidona/química , Povidona/metabolismo , Piel/metabolismo , Porcinos
18.
Aquat Toxicol ; 173: 94-104, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26854872

RESUMEN

Nanomaterials of various shapes and dimensions are widely used in the medical, chemical, and electronic industries. Multiple studies have reported the ecotoxicological effects of nanaoparticles when released in aquatic and terrestrial ecosystems; however, information on the toxicity of silver nanowires (AgNWs) to freshwater organisms and their transfer through the food webs is limited. In the present study, we aimed to evaluate the toxicity of 10- and 20-µm-long AgNWs to the alga Chlamydomonas reinhardtii, the water flea Daphnia magna, and the zebrafish and study their movement through this three-species food chain using a variety of qualitative and quantitative methods as well as optical techniques. We found that AgNWs directly inhibited the growth of algae and destroyed the digestive organs of water fleas. The results showed that longer AgNWs (20µm) were more toxic than shorter ones (10µm) to both algae and water fleas, but shorter AgNWs were accumulated more than longer ones in the body of the fish. Overall, this study suggests that AgNWs are transferred through food chains, and that they affect organisms at higher trophic levels, potentially including humans. Therefore, further studies that take into account environmental factors, food web complexity, and differences between nanomaterials are required to gain better understanding of the impact of nanomaterials on natural communities and human health.


Asunto(s)
Chlamydomonas reinhardtii/efectos de los fármacos , Daphnia/efectos de los fármacos , Cadena Alimentaria , Nanocables/toxicidad , Povidona/toxicidad , Plata/toxicidad , Pez Cebra/metabolismo , Animales , Organismos Acuáticos/efectos de los fármacos , Organismos Acuáticos/metabolismo , Daphnia/metabolismo , Tracto Gastrointestinal/efectos de los fármacos , Tamaño de la Partícula , Povidona/metabolismo , Plata/metabolismo , Contaminantes Químicos del Agua/metabolismo , Contaminantes Químicos del Agua/toxicidad
19.
AAPS J ; 18(2): 416-23, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26769250

RESUMEN

Previous studies suggested that an amorphous solid dispersion with a copolymer consisting of both hydrophobic and hydrophilic monomers could improve the dissolution profile of a poorly water-soluble drug compared to the crystalline form. Therefore, this study investigated the influence of the copolymer composition of polyvinylpyrrolidone/vinyl acetate (PVP/VA) on the non-sink in vitro dissolution behavior and in vivo performance of celecoxib (CCX) amorphous solid dispersions. The study showed that the hydrophilic monomer vinylpyrrolidone (VP) was responsible for the generation of CCX supersaturation whereas the hydrophobic monomer vinyl acetate (VA) was responsible for the stabilization of the supersaturated solution. For CCX, there was an optimal copolymer composition around 50-60% VP content where further replacement of VP monomers with VA monomers did not have any biopharmaceutical advantages. A linear relationship was found between the in vitro AUC(0-4h) and in vivo AUC(0-24h) for the CCX:PVP/VA systems, indicating that the non-sink in vitro dissolution method applied in this study was useful in predicting the in vivo performance. These results indicated that when formulating a poorly water-soluble drug as an amorphous solid dispersion using a copolymer, the copolymer composition has a significant influence on the dissolution profile and in vivo performance. Thus, the dissolution profile of a drug can theoretically be tailored by changing the monomer ratio of a copolymer with respect to the required in vivo plasma-concentration profile. As this ratio is likely to be drug dependent, determining the optimal ratio between the hydrophilic (dissolution enhancing) and hydrophobic (crystallization inhibiting) monomers for a given drug is imperative.


Asunto(s)
Celecoxib/química , Polímeros/química , Povidona/química , Compuestos de Vinilo/química , Animales , Celecoxib/sangre , Química Farmacéutica , Masculino , Polímeros/metabolismo , Povidona/metabolismo , Ratas , Ratas Sprague-Dawley , Solubilidad , Compuestos de Vinilo/sangre , Difracción de Rayos X
20.
ACS Nano ; 10(1): 93-101, 2016 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-26592739

RESUMEN

Because of the aggressive and recurrent nature of cancers, repeated and multimodal treatments are often necessary. Traditional cancer therapies have a risk of serious toxicity and side effects. Hence, it is crucial to develop an alternative treatment modality that is minimally invasive, effectively treats cancers with low toxicity, and can be repeated as required. We developed a light-activatable microneedle (MN) system that can repeatedly and simultaneously provide photothermal therapy and chemotherapy to superficial tumors and exert synergistic anticancer effects. This system consists of embeddable polycaprolactone MNs containing a photosensitive nanomaterial (lanthanum hexaboride) and an anticancer drug (doxorubicin; DOX), and a dissolvable poly(vinyl alcohol)/polyvinylpyrrolidone supporting array patch. Because of this supporting array, the MNs can be completely inserted into the skin and embedded within the target tissue for locoregional cancer treatment. When exposed to near-infrared light, the embedded MN array uniformly heats the target tissue to induce a large thermal ablation area and then melts at 50 °C to release DOX in a broad area, thus destroying tumors. This light-activated heating and releasing behavior can be precisely controlled and switched on and off on demand for several cycles. We demonstrated that the MN-mediated synergistic therapy completely eradicated 4T1 tumors within 1 week after a single application of the MN and three cycles of laser treatment. No tumor recurrence and no significant body weight loss of mice were observed. Thus, the developed light-activatable MN with a unique embeddable feature offers an effective, user-friendly, and low-toxicity option for patients requiring long-term and multiple cancer treatments.


Asunto(s)
Antineoplásicos/farmacología , Terapia Combinada/métodos , Doxorrubicina/farmacología , Elementos de la Serie de los Lantanoides/química , Neoplasias Cutáneas/terapia , Animales , Línea Celular Tumoral , Liberación de Fármacos , Femenino , Humanos , Hipertermia Inducida/instrumentación , Hipertermia Inducida/métodos , Inyecciones Intralesiones , Inyecciones Subcutáneas , Rayos Láser , Nanopartículas del Metal/administración & dosificación , Nanopartículas del Metal/química , Ratones , Ratones SCID , Agujas , Fototerapia/instrumentación , Fototerapia/métodos , Poliésteres/metabolismo , Alcohol Polivinílico/metabolismo , Povidona/metabolismo , Neoplasias Cutáneas/patología
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