Advanced Inorganic Nanosystems for Skin Drug Delivery.

On/into/through the skin drug delivery represents an attractive alternative for the oral route, providing local and/or systemic drug delivery. Due to its complex and well-organised structure, most of the drugs show difficulties to penetrate the human skin. Therefore, enormous efforts have been invested to develop intelligent drug delivery systems overcoming the skin barrier with particular emphasis on increasing therapeutic activity and minimizing undesirable side-effects. Most of these strategies require the use of singular materials with new properties. In particular, and on the basis of their inherent properties, including biocompatibility, biodegradability and relative low-cost, inorganic nanoparticles are ideal candidates for the development of skin drug delivery systems. This review provides an updated and comprehensive overview of the state of the art in the trends towards skin drug delivery with a particular focus in the attractive alternative offered by inorganic-based nanosystems.

Assessment of halloysite nanotubes as vehicles of isoniazid.

Equilibrium and thermodynamic aspects of the adsorption of isoniazid (INH) onto halloysite nanotubes (HLNTs) and characteristics of the resultant drug/nanocarrier systems are investigated. Equilibrium studies were performed in aqueous medium at different times, temperatures and drug concentrations. The overall adsorption process was explained as the result of two simple processes: adsorption on the activated sites of HLNTs and precipitation of INH on HLNTs surface. Formation of the INH-loaded HLNTs was spontaneous, endothermic and endoentropic, increasing the thermodynamic stability of the system (ΔH=70.40kJ/mol; ΔS=0.2519kJ/molK). Solid state characterization corroborated the effective interaction between the components that was also described by modeling at molecular level by quantum mechanics calculations along with empirical interatomic potentials. Transmission electron microphotographs confirmed the double allocation and homogeneous distribution of INH in the nanohybrids. FTIR spectra revealed the interaction via hydrogen bonds between the inner hydroxyl groups of HLNTs and N in INH molecules. Loading of INH in the nanohybrids was approximately 20% w/w. Effective loading of INH and activation energies of the interactions enable to propose the designed nanohybrids in the development of modified drug delivery systems.

Release kinetics of 5-aminosalicylic acid from halloysite.

This paper investigates desorption of 5-aminosalicilyc acid (5-ASA) adsorbed onto halloysite (HL). Desorption isotherms were fitted according to kinetic laws obtained considering release of 5-ASA from HL as the phase of desorption of the previously adsorbed drug molecules both inside the nanotubes of HL as onto the surface of clay particles and/or in the inter-particle spaces of their aggregates. Desorption isotherms has been also fitted with other equations frequently used in drug release kinetics studies. The best fitting corresponded to the kinetic model proposed; in agreement with the results of adsorption.

One-dimensional filtration of pharmaceutical grade phyllosilicate dispersions.

The filtration behaviour of some clay-water dispersions was studied. Two Spanish fibrous phyllosilicates (sepiolite from Vicálvaro and palygorskite from Turón) and a commercial bentonite (Bentopharm UK) with similar sizes and different morphologies (fibrous and/or laminar) were selected as model clays. Sepiolite from Vicálvaro is an almost pure fibrous sample, Bentopharm presents a high amount of laminar particles and palygorskite from Turón is made up of similar percentages of laminar and fibrous particles. The disperse systems were made up using a rotor-stator mixer working at two different mixing rates (1000 and 8000 rpm), for periods of 1 and 10 min. Filtration measurements were taken and the corresponding filtration curves obtained. Finally, the desorptivity (S) of the filtration cakes was calculated and correlated to the textural characteristics of the materials, the solid fraction and mixing conditions. Filtration behaviour of the dispersions depended on all three of these factors. Laminar dispersions presented lower S values than fibrous dispersions. In the 2% w/v dispersions the bridging forces between particles did not permit formation of an interconnected network as in 10% w/v dispersions and, consequently, filtration times increased with the solid fraction (i.e. S values decreased). Regarding stability to pH changes, the results showed that filtration behaviour was highly sensitive to basic pH in the fibrous clay dispersions and almost insensitive in the laminar clay dispersions.

La sedación no protocolizada en una Unidad de Medicina Intensiva / Non-Protocolized Sedation In The Intensive Care Unit

Objetivo. Estudio descriptivo de la sedación y de su efectividad, en un Servicio de Medicina Intensiva (SMI) que no dispone de protocolización en su uso. Método. En todos los pacientes ingresados en el SMI entre enero y mayo de 1998 sometidos a ventilación mecánica y a los que su médico había decidido sedar, se recogieron datos acerca de los requerimientos de ventilación mecánica, nivel de sedación del paciente (escala de Ramsay), dosis diarias del fármaco (mg/kg/día) utilizado, y tiempo requerido entre la retirada de sedación e inicio de weaning. Para evitar la variabilidad entre turnos, los datos se recogieron una vez por turno y siempre a la misma hora. El personal del SMI no fue avisado de la realización del estudio. Resultados. En total se recogieron 50 pacientes. El nivel medio de sedación aplicado en 648 determinaciones según la escala de Ramsay fue de 5,2 (1,1), variable no relacionada significativamente con las necesidades de ventilación mecánica. Las dosis medias de midazolam fueron 3,41 mg/kg/día. La tasa de autoextubación fue del 0 por ciento. Por otro lado, el tiempo requerido desde la retirada de la sedación hasta el despertar del paciente fue de 21 horas (mediana). No hubo diferencias estadísticamente significativas entre las dosis de midazolam recibidas, nivel de sedación e intervalo retirada sedación-inicio weaning, entre los pacientes que presentaron o no insuficiencia renal. Conclusiones. Si no se protocoliza la sedación en el SMI, existe una tendencia a dejar al paciente en niveles cercanos al coma profundo (AU)