Nutriosomes: prebiotic delivery systems combining phospholipid, soluble dextrin and curcumin to counteract intestinal oxidative stress and inflammation

Nutriosomes, new phospholipid nanovesicles specifically designed for intestinal protection were developed by simultaneously loading a water-soluble dextrine (Nutriose® FM06) and a natural antioxidant (curcumin). Nutriosomes were easily fabricated in a one-step, organic solvent-free procedure. The stability and the delivery performances of the vesicles were improved by adding hydroxypropylmetylcellulose. All the vesicles were small in size (mean diameter ~168 nm), negatively charged (zeta potential ~-38 mV, irrespective of their composition), self-assembled predominantly in unilamellar vesicles stabilized by the presence of Nutriose® , which was located in both the inter-lamellar and inter-vesicle medium, as confirmed by cryo-TEM and SAXS investigation. The dextrin acted also as a cryo-protector, avoiding vesicle collapse during the lyophilization process, and as a protector against high ionic strength and pH changes encountered in the gastrointestinal environment. Thanks to the antioxidant properties of curcumin, nutriosomes provided an optimal protective effect against hydrogen peroxide-induced oxidative stress in Caco-2 cells. Moreover, these innovative vesicles showed promising efficacy in vivo, as they improved the bioavailability and the biodistribution of both curcumin and dextrin upon oral administration, which acted synergically in reducing colonic damage chemically-induced in rats

Famílies botàniques de plantes medicinals

Facultat de Farmàcia, Universitat de Barcelona. Ensenyament: Grau de Farmàcia, Assignatura: Botànica Farmacèutica, Curs: 2013-2014, Coordinadors: Joan Simon, Cèsar Blanché i Maria Bosch.Els materials que aquí es presenten són els recull de 175 treballs d’una família botànica d’interès medicinal realitzats de manera individual. Els treballs han estat realitzat per la totalitat dels estudiants dels grups M-2 i M-3 de l’assignatura Botànica Farmacèutica durant els mesos d’abril i maig del curs 2013-14. Tots els treballs s’han dut a terme a través de la plataforma de GoogleDocs i han estat tutoritzats pel professor de l’assignatura i revisats i finalment co-avaluats entre els propis estudiants. L’objectiu principal de l’activitat ha estat fomentar l’aprenentatge autònom i col·laboratiu en Botànica farmacèutica

Pasados y presente. Estudios para el profesor Ricardo García Cárcel

Ricardo García Cárcel (Requena, 1948) estudió Historia en Valencia bajo el magisterio de Joan Reglà, con quien formó parte del primer profesorado de historia moderna en la Universidad Autónoma de Barcelona. En esta universidad, desde hace prácticamente cincuenta años, ha desarrollado una extraordinaria labor docente y de investigación marcada por un sagaz instinto histórico, que le ha convertido en pionero de casi todo lo que ha estudiado: las Germanías, la historia de la Cataluña moderna, la Inquisición, las culturas del Siglo de Oro, la Leyenda Negra, Felipe II, Felipe V, Austrias y Borbones, la guerra de la Independencia, la historia cultural, los mitos de la historia de España... Muy pocos tienen su capacidad para reflexionar, ordenar, analizar, conceptualizar y proponer una visión amplia y llena de matices sobre el pasado y las interpretaciones historiográficas. A su laboriosidad inimitable se añade una dedicación sin límites en el asesoramiento de alumnos e investigadores e impulsando revistas, dosieres, seminarios o publicaciones colectivas. Una mínima correspondencia a su generosidad lo constituye este volumen a manera de ineludible agradecimiento

Modelización farmacocinética de la taurina: influencia del estado nutricional

La desnutrición es una alteración fisiológica que cursa con modificaciones en la función corporal y está asociada a determinados procesos quirúrgicos, cáncer y enfermedades metabólicas1. Los requerimientos de taurina, aminoácido condicionalmente esencial, aumentan en estados patológicos, y sus parámetros farmacocinéticos pueden verse alterados en estado de desnutrición2. El objetivo de este trabajo es analizar la influencia de la desnutrición calórico proteica sobre los parámetros farmacocinéticos de taurina en rata y evaluar el valor añadido que supone la administración de un suplemento de taurina en una dieta enteral comercial (T Diet Plus®, TDP) respecto a otra no suplementada (Isosource Estándar® IST). Los ensayos, en ratas Wistar, han sido aprobados por el Comité Ético de la Facultad de la Universidad de Valencia. Los animales se distribuyen de forma aleatoria en dos grupos y durante un periodo de 26 días se alimentan en condiciones controladas: grupo normonutrido (NN) (dieta estándar con un 14% de proteína y 62 Kcal/día) y grupo desnutrido (DN) (dieta con un 5% de proteína y 38 Kcal/día)3. La taurina se administra en dosis única de 1, 10 ó 100 mg por vía intravenosa u oral, obteniendo un total de 12 subgrupos (6 NN y 6 DN). Se toman muestras de sangre a tiempos prefijados a través de una cánula implantada en la vena yugular y se analiza el contenido de taurina mediante HPLC. El análisis matemático de las concentraciones plasmáticas de taurina se ha realizado mediante el modelo no lineal de efectos mixtos a través de la regresión no lineal por mínimos cuadrados extendidos, con doble precisión y estimación de primer orden, implementada en el software NONMEM 7. Se han evaluado los modelos mono y bicompartimental y se ha estudiado la influencia de las covariables estado nutricional, peso y albúmina plasmática sobre los parámetros farmacocinéticos. Asimismo, a otro grupo de animales (6 NN y 6 DN) se les ha administrado agua y dos dietas enterales comerciales (TDP, enriquecida con taurina; e IST, no enriquecida) en régimen de dosis única y dosis múltiple, valorando la exposición al aminoácido y el valor añadido de a dieta suplementada mediante el cálculo del Tmax, Cmax y AUC. El modelo farmacocinético que mejor predice los datos experimentales de concentración plasmática de taurina vs tiempo es el bicompartimental en el que la concentración basal del aminoácido se modela mediante una velocidad de orden cero, la distribución entre el compartimento central y periférico mediante una cinética de primer orden y aclaramiento no lineal compuesto por secreción tubular activa y reabsorción tubular activa, en el que la capacidad del proceso de secreción disminuye en estado de desnutrición aproximadamente un 10%. Cuando la taurina se administra por vía oral, el proceso de absorción se describe como un proceso de primer orden que no se modifica en estado de desnutrición. La administración de la dieta enteral suplementada con taurina libre TDP en régimen de dosis múltiple, incrementa los niveles plasmáticos del aminoácido por encima de los niveles basales en estado de desnutrición

Relevance of Therapeutic Drug Monitoring of Tyrosine Kinase Inhibitors in Routine Clinical Practice: A Pilot Study

Introduction: The main goal of treatment in cancer patients is to achieve the highest therapeutic effectiveness with the least iatrogenic toxicity. Tyrosine kinase inhibitors (TKIs) are anticancer oral agents, usually administered at fixed doses, which present high inter- and intra-individual variability due to their pharmacokinetic characteristics. Therapeutic drug monitoring (TDM) can be used to optimize the use of several types of medication. Objective: We evaluated the use of TDM of TKIs in routine clinical practice through studying the variability in exposure to erlotinib, imatinib, lapatinib, and sorafenib and dose adjustment. Materials and methods: We conducted a retrospective analytical study involving patients who received treatment with TKIs, guided by TDM and with subsequent recommendation of dose adjustment. The quantification of the plasma levels of the different drugs was performed using high-performance liquid chromatography (HPLC). The Clinical Research Ethics Committee of the Hospital Quirónsalud Torrevieja approved this study. Results: The inter-individual variability in the first cycle and in the last monitored cycle was 46.2% and 44.0% for erlotinib, 48.9 and 50.8% for imatinib, 60.7% and 56.0% for lapatinib and 89.7% and 72.5% for sorafenib. Relationships between exposure and baseline characteristics for erlotinib, imatinib, lapatinib and sorafenib were not statistically significant for any of the variables evaluated (weight, height, body surface area (BSA), age and sex). Relationships between height (p = 0.021) and BSA (p = 0.022) were statistically significant for sorafenib. No significant relationships were observed between Ctrough and progression-free survival (PFS) or overall survival (OS) for any drug, except in the case of sunitinib (correlation between Ctrough and PFS p = 0.023) in the exposure–efficacy analysis. Conclusions: Erlotinib, imatinib, lapatinib and sorafenib show large inter-individual variability in exposure. TDM entails a significant improvement in exposure and enables more effective and safe use of TKIs in routine clinical practice

Effects of ethanol and diclofenac on the organization of hydrogenated phosphatidylcholine bilayer vesicles and their ability as skin carriers

In this study, the effects of ethanol and/or diclofenac on vesicle bilayer structure have been studied. Liposomes with hydrogenated soy phosphatidylcholine, cholesterol and two different concentrations of diclofenac sodium (5 and 10 mg/ml) were obtained. In addition, ethanol was mixed in the water phase at different concentrations (5, 10 and 20 % v/v) to obtain ethosomes. To characterize vesicles, rehological analysis were carried out to investigate the intervesicle interactions, while bilayer structure was evaluated by small-and wide-angle X-ray scattering. Finally, the ethanol and/or diclofenac concentration-dependent ability to improve diclofenac skin delivery was evaluated in vitro. The addition of 20 % ethanol and/or diclofenac led to solid-like ethosome dispersion due to the formation of a new intervesicle structure, as previously found in transcutol containing vesicle dispersions. However, when using 5-10 % of ethanol the induction to form vesicle interconnections was less evident but the simultaneous presence of the drug at the highest concentration facilitated this phenomenon. Ethosomes containing the highest amount of both, drug (10 mg/ml) and ethanol (20 % v/v), improved the drug deposition in the skin strata and in the receptor fluid up to 1.5-fold, relative to liposomes. Moreover this solid-like formulation can easily overcome drawbacks of traditional liquid liposome formulations which undergo a substantial loss at the application site

Phycocyanin-encapsulating hyalurosomes as carrier for skin delivery and protection from oxidative stress damage

Abstract: The phycobiliprotein phycocyanin, extracted from Klamath algae, possesses important biological properties but it is characterized by a low bioavailability due to its high molecular weight. To overcome the bioavailability problems, phycocyanin was successfully encapsulated, using an environmentally-friendly method, into hyalurosomes, a new kind of phospholipid vesicles immobilised with hyaluronan sodium salt by the simple addition of drug/sodium hyaluronate water dispersion to phospholipids. Liposomes were used as a comparison. Vesicles were small in size and homogeneously dispersed, being the mean size always smaller than 150 nm and PI never higher than 0.31. Liposomes were unilamellar and spherical, the addition of the polymer slightly modify the vesicular shape which remain spherical, while the addition of PEG improve the lamellarity of vesicles being multilamellar vesicles. In all cases phycocyanin was encapsulated in good amount especially using hyalurosomes and PEG hyalurosomes (65 and 61 % respectively). In vitro penetration studies suggested that hyalurosomes favoured the phycocyanin deposition in the deeper skin layers probably thanks to their peculiar hyaluronan–phospholipid structure. Moreover, hyalurosomes were highly biocompatible and improved phycocyanin antioxidant activity on stressed human keratinocytes respect to the drug solution. Graphical Abstract: [Figure not available: see fulltext.