Improvement of imiquimod solubilization and skin retention via tpgs micelles: Exploiting the co-solubilizing effect of oleic acid

Imiquimod (IMQ) is an immunostimulant drug approved for the topical treatment of actinic keratosis, external genital-perianal warts as well as superficial basal cell carcinoma that is used off-label for the treatment of different forms of skin cancers, including some malignant melanocytic proliferations such as lentigo maligna, atypical nevi and other in situ melanoma-related diseases. Imiquimod skin delivery has proven to be a real challenge due to its very low water-solubility and reduced skin penetration capacity. The aim of the work was to improve the drug solubility and skin retention using micelles of d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), a water-soluble derivative of vitamin E, co-encapsulating various lipophilic compounds with the potential ability to improve imiquimod affinity for the micellar core, and thus its loading into the nanocarrier. The formulations were characterized in terms of particle size, zeta potential and stability over time and micelles performance on the skin was evaluated through the quantification of imiquimod retention in the skin layers and the visualization of a micelle-loaded fluorescent dye by two-photon microscopy. The results showed that imiquimod solubility strictly depends on the nature and concentration of the co-encapsulated compounds. The micellar formulation based on TPGS and oleic acid was identified as the most interesting in terms of both drug solubility (which was increased from few µg/mL to 1154.01 ± 112.78 µg/mL) and micellar stability (which was evaluated up to 6 months from micelles preparation). The delivery efficiency after the application of this formulation alone or incorporated in hydrogels showed to be 42-and 25-folds higher than the one of the commercial creams

A π-Extended Donor-Acceptor-Donor Triphenylene Twin linked via a Pyrazine-bridge

Beta-amino triphenylenes can be accessed via palladium catalyzed amination of the corresponding triflate using benzophe-none imine. Transformation of amine 6 to benzoyl amide 18 is also straightforward and its wide mesophase range demon-strates that the new linkage supports columnar liquid crystal formation. Amine 6 also undergoes clean aerobic oxidation to give a new twinned structure linked through an electron-poor pyrazine ring. The new discotic liquid crystal motif contains donor and acceptor fragments, and is more oval in shape rather than disk-like. It forms a wide range columnar mesophase. Absorption spectra are strong and broad; emission is also broad and occurs with a Stokes shift of ca. 0.7 eV, indicative of charge-transfer characte

Micro- or nanoseparated phases in thermoset blends of an epoxy resin and PEO–PPO–PEO triblock copolymer

Diaminodiphenylmethane (DDM) curing at several temperatures of a diglycidyl ether of bisphenol A (DGEBA) epoxy resin modified with a poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide) (PEO–PPO–PEO) block copolymer has been investigated in order to characterize the miscibility and morphological features. Two distinct phases are present for every blends studied except for DGEBA/DDM modified with 10 wt% PEO–PPO–PEO and cured at low temperature. Depending on the curing condition, phase separation takes place at micro or nanoscale due to competition among kinetic and thermodynamic factors. The mechanistic approach used for modeling the curing reactions shows that the formation of epoxy–hydroxyl complex and the auto catalytic process are slightly decreased whilst the noncatalytic process is favoured upon copolymer addition. Modifier addition delays curing process as the influence of both formation of epoxy–hydroxyl complex and catalytic process on reaction rate is higher than the influence of noncatalytic process. A thermodynamic model describing a thermoset/block copolymer considered as only one entity system is proposed. The LCST behaviour allows to elucidate nano or micro separated structures obtained at low and high curing temperatures, respectively.Fil: Larrañaga, M.. Universidad del País Vasco; EspañaFil: Gabilondo, N.. Universidad del País Vasco; EspañaFil: Kortaberria, G.. Universidad del País Vasco; EspañaFil: Serrano, E.. Universidad del País Vasco; EspañaFil: Remiro, P.. Universidad del País Vasco; EspañaFil: Riccardi, Carmen Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; ArgentinaFil: Mondragon, I.. Universidad del País Vasco; Españ

An Alternative Device for the Topical Treatment of Oral Cancer: Development and Ex-Vivo Evaluation of Imiquimod-Loaded Polysaccharides Formulations

The topical use of imiquimod (IMQ), a non-specific immune response modifier, showed to be a promising therapeutic option for the early-stage treatment of some type of oral cancer, even when performed with a formulation (Aldara(R)) developed and approved for skin application. The aim of this work was the development of buccal formulations for the topical administration of IMQ with improved mucosal retention and reduced trans-mucosal permeation when compared to the reference formulation. Three different hydrogels based on carboxymethyl chitosan (CMChit), sodium alginate (A), and xanthan gum (X) in different combinations were prepared, and the loading of imiquimod was successfully performed by using a micellar formulation based on d-alpha-tocopheril polyethylene glycol 100 succinate (TPGS). Except for CMChit formulation, in all the other cases, the performance in vitro on the mucosa resulted comparable to the commercial formulation, despite the drug loading being 50-fold lower. Converting the gels in films did not modify the IMQ accumulated with respect to the correspondent gel formulation but produced as a positive effect a significant reduction in the amount permeated. Compared to the commercial formulation, this reduction was significant (p < 0.01) in the case of X film, resulting in an improvement of the retained/permeated ratio from 1 to 5.44. Mucoadhesion evaluation showed similar behavior when comparing the developed gels and the commercial formulation, and an excellent bioadhesion was observed for the films

Resonant spin tunneling in small antiferromagnetic particles

The paper reports a detailed experimental study on magnetic relaxation of natural horse-spleen ferritin. ac susceptibility measurements performed on three samples of different concentration show that dipole-dipole interactions between uncompensated moments play no significant role. Furthermore, the distribution of relaxation times in these samples has been obtained from a scaling of experimental X" data, obtained at different frequencies. The average uncompensated magnetic moment per protein is compatible with a disordered arrangement of atomic spins throughout the core, rather than with surface disorder. The observed field dependence of the blocking temperature suggests that magnetic relaxation is faster at zero field than at intermediate field values. This is confirmed by the fact that the magnetic viscosity peaks at zero field, too. Using the distribution of relaxation times obtained independently, we show that these results cannot be explained in terms of classical relaxation theory. The most plausible explanation of these results is the existence, near zero field, of resonant magnetic tunneling between magnetic states of opposite orientation, which are thermally populated

Programa Comunitario de Educación Especial en Cantabria : informe del tercer año de trabajos

Continuar con la labor asistencial con un incremento del 400 por 100 con relación al primer año, continuación de la tarea de reciclaje y formación, realización y resultados de una campaña de comarcalización. El objeto del trabajo durante el último año del equipo de Educación Especial en Cantabria han sido tareas asistenciales, tareas de reciclaje y formación y tareas de investigación. Este proyecto ha intentado llegar a las personas que necesitan ayuda, aportando soluciones a través de la investigación y el avance de los conocimientos en el tema. Se han realizado encuestas y cuestionarios en distintos colegios de la comarca sobre los siguientes temas: intervención en crisis y prevención secundaria, tareas de reciclaje y formación, personalidad, participación y éxito terapéutico en un modelo de mediadores y la integración de deficientes en la sociedad. Análisis estadístico de todos los datos recogidos, análisis factorial de factores principales con posterior petición de rotación Varimax de Kaiser para aquellos factores que posean un valor propio igual o mayor a 1,00. Análisis factorial de la escala F. Análisis factorial de la escala DO. Análisis factorial de la escala AA. Se deben tener en cuenta variables de personalidad y motivación, tanto para la implantación de programas de acción social como para la implementación de su eficacia. Se presentan los resultados factoriales de las dimensiones socio-actitudinales de la personalidad. La autoimplicación y aceptación de la integración y las dimensiones sociales de la personalidad y aceptación de la integración. El equipo de trabajo recomienda utilizar y explotar al máximo de sus posibilidades los modelos asistenciales de mediadores y la necesidad de ofrecer una pluralidad de servicios asistenciales con el fin de que puedan llegar al mayor volumen posible de ciudadanos los programas de ayuda que se gestan.CantabriaES