Biocerámicos: aspectos farmaco-tecnológicos y clínicos de uso odontológico / Bioceramics: pharmatechnological and clinical aspects of dental use

Se analizan aspectos fármaco-tecnológicos y clínicos de biocerámicos bioabsorbibles compuestos por biovidrios con capacidad osteogénica y microbicida, para ser utilizados como relleno bioactivo en el conducto radicular y como tratamiento terapéutico en el sitio de a lesión apicoperirradicular de origen endodóntico. Mediante un diagrama ternario se consideraron las diversas variables cuyos valores determinan las diferentes fases de los vidrios bioactivos, hasta alcanzar la formación de hidroxiapatita, cuando se someten a un medio biológico. Se analizaron composición y mecanismo de acción en la reparación posendodóntica, que parte de la integración del biomaterial al tejido duro sano, sin formación de fibrosis o proceso inflamatorio inmune (AU)

Pharmacotechnological and clinical aspects of bioabsorbable bioceramics composed of bioglasses with osteogenic and microbicidal capacity are analyzed, to be used as a bioactive filler in the root canal and as a therapeutic treatment at the site of an apicoperiradicular lesion of endodontic origin. By means of a ternary diagram, the various variables whose values determine the different phases of the bioactive glasses were considered, until reaching the formation of hydroxyapatite, when subjected to a biological medium. Composition and mechanism of action were analyzed in post-endodontic repair, which starts from the integration of the biomaterial into healthy hard tissue, without the formation of fibrosis or an immune inflammatory process (AU)

Antibacterial activity of essential oils of aloysia polystachya and lippia turbinata (Verbenaceae) / Actividad antibacteriana de los aceites esenciales de aloysia polystachya y lippia turbinata (Verbenaceae)

Aloysia polystachya and Lippia turbinata are medicinal and aromatic plants. Nevertheless, there are few reports in literature concerning the biological properties of species that grow in northeastern Argentina. The antibacterial activity and the chemical composition of both essential oils were evaluated in this work. The extraction was performed by steam distillation and their volatile compounds were determined by gas chromatography/mass spectrometry. The antibacterial activity was evaluated by disc diffusion and broth microdilution assay. The main compounds were carvone (78.9 percent) and limonene (14.2 percent) in A. polystachya and carvone (80.77 percent), limonene (8.73 percent), beta- caryophyllene (2.13 percent) and 1,8-cineole (1.70 percent) in L. turbinata. Both essential oils were bactericide against Escherichia coli ATCC 35218 and clinical isolates of Enterobacter cloacae and Klebsiella pneumoniae. Essential oil of A. polystachya was also bactericide against Staphylococcus aureus ATCC 29212, S. aureus ATCC 25923 and clinical strain of S. aureus methicillin susceptible.

Aloysia polystachya y Lippia turbinata son plantas medicinales y aromáticas. Hay pocos informes en la literatura sobre las propiedades biológicas de especies que crecen en el nordeste de Argentina. La actividad antibacteriana y la composición química de ambas especies se evaluaron en este trabajo. La extracción se realizó por destilación con vapor y sus compuestos se determinaron por cromatografía gaseosa/espectrometría de masa. La actividad antibacteriana fue evaluada por difusión en discos y microdilución en caldo. Los principales compuestos fueron carvona (78.9 por ciento) y limoneno (14.2 por ciento) en A. polystachya y carvona (80.77 por ciento), limoneno (8.73 por ciento), beta-cariofileno (2.13 por ciento) y 1,8-cineol (1.70 por ciento) en L. turbinata. Ambos aceites esenciales fueron activos contra Escherichia coli ATCC 35218 y aislamientos clínicos de Enterobacter cloacae y Klebsiella pneumoniae. El aceite esencial de A. polystachya fue bactericida contra Staphylococcus aureus ATCC 29212, S. aureus ATCC 25923 y aislamientos clínicos de S. aureus sensible a meticilina.

Estudio de la estabilidad de emulsiones con estructuras líquido-cristalinas, y su aplicación farmacéutica mediante el agregado de un principio activo liposoluble: Econazol / Study of emulsions stability with liquid crystals structure and their pharmaceutical application by the addition of a liposoluble principe active: Econazole

La piel es un órgano apropiado para administrar principios activos con el fin de obtener efectos locales o sistémicos. Las formulaciones de uso tópico más comunes son: lociones, emulsiones, suspensiones, cremas, pomadas; las cuales deben reunir determinadas condiciones para ser aplicadas sobre la piel. El objetivo del presente trabajo es seleccionar una emulsión preparada con la técnica de formación de cristales líquidos compuesta de ácido esteárico, vaselina líquida, trietanolamina, propilparabeno, metilparabeno y agua, a la que se le incorpora un ingrediente farmacéutico activo liposoluble: econazol. El econazol, principio activo cuya vía de administración es la tópica y su acción es local, es una sustancia soluble en aceites, que se aloja en la fracción liposoluble de los cristales líquidos y en la fase interna de la emulsión sin que se modifique el perfil reológico ni la estabilidad de los sistemas. Se estudió además del HLB y de sus comportamientos reológicos, la presencia de cristales líquidos con luz polarizada, la existencia de gotas secundarias con luz común y la estabilidad de los sistemas por centrifugación y estrés térmico a temperaturas de 40 ºC. Los valores obtenidos en los estudios realizados, demostraron que la emulsión lograda presenta un perfil reológico y las condiciones de estabilidad adecuadas para ser utilizada como crema medicinal.

The skin is the appropiate organ to administrate active principles in orden to obtain local or systemic effects. Formulations for topical use most common are: lotions, emulsions, suspensions, creams, ointments, which must gather certain conditions to be applied to the skin. In this work, the objective is to select an emulsion prepared by a technique of liquid crystals formation composed by stearic acid, mineral oil, triethanolamine, propylparaben, methylparaben and water. To this formula we incorporated a pharmaceutical active liposoluble ingredient: econazole. Econazole, a principle active with topical administration and local action, is a substance soluble in oils, which stays in the liposoluble fraction of the liquid crystals and in their internal phase of the emulsion without modifying their rheological profile not even the stability of systems. Besides the HLB of the systems and their rheological behaviour we also study the presence of liquid crystals with polarized light, the existence of secondary drops with common light and systems stability by centrifugation, thermal stress and temperatures of 40 °C. The values obtained from the studies made, demonstrated that the emulsion achieved present a rheological profile and stability conditions suitable for medicinal use cream.

Novel gel-like microemulsion for topical delivery of Amphotericin B / Una nueva microemulsión tipo gel para la aplicación tópica de anfotericina B

The aim of the present work was to develop a ME for topical delivery of Amphotericin B (AmB). Microemulsions (MEs) are versatile systems to solubilize drugs due to the presence of both a hydrophobic and a hydrophilic region, as well as a distinctive interface composed of surfactant and cosurfactant. MEs have been reported for many advantages for topical application of drugs. Considering that AmB has very low water solubility a screening of surfactants and oils was performed. A gel-like ME system, that can be applied topically without the need for thickeners agents, was selected. AmB was incorporated up to 1 mg/g and remained stable for at least 90 days both at 4 °C and room temperature, so this formulation would be appropriate as a compounding medication. An in vitro skin penetration test was performed, the applied dose penetrated (10.16 +/- 0.01 µg/cm²/h as estimated flux) and remained completely within the skin during the assay; AmB was not detected in the receptor compartment. In vitro antifungal and antileishmanial activity was tested and drug showed proper activity. AmB is a second line drug for the treatment of cutaneous leishmaniasis, but topical dosage forms are still lacking. This system is potentially useful for the treatment of skin infections avoiding drug toxic systemic effects.

Se desarrolló una microemulsión (ME) para la aplicación tópica de anfotericina B (AmB). Las ME son sistemas versátiles que facilitan la solubilización de principios activos y, además, presentan muchas ventajas para aplicar fármacos en forma tópica. La AmB posee muy baja solubilidad en agua, por lo cual se realizó una evaluación de su solubilidad en distintos aceites y surfactantes. Se confeccionaron diagramas ternarios de fase y se seleccionó una ME-gel que puede ser aplicada tópicamente sin el agregado de agentes espesantes. Se solubilizó hasta 1 mg/g de AmB y el fármaco permaneció estable durante al menos 90 días a 4 °C y a temperatura ambiente, por lo cual esta formulación sería apropiada como un medicamento magistral. El estudio in vitro de permeación en piel mostró que la dosis aplicada penetró completamente (flujo estimado de difusión 10,16 +/- 0,01 µg/cm²/h) y permaneció retenida en la misma durante el tiempo de estudio sin detectarse AmB en el compartimento receptor. La actividad antifúngica y antileishmania in vitro fue adecuada. La AmB es una droga de segunda línea en el tratamiento de la leishmaniasis cutánea; sin embargo, no se dispone de preparados para uso tópico. Esta formulación sería útil para el tratamiento local de las infecciones de piel, evitando efectos adversos sistémicos.

Pharmaceutical optimization of lipid-based dosage forms for the improvement of taste-masking, chemical stability and solubilizing capacity of phenobarbital.

Microemulsions (MEs) and self-emulsifying drug delivery systems (SEEDS) containing phenobarbital (Phe) were developed to improve its chemical stability, solubilizing capacity and taste-masking in oral liquid dosage forms. Cremophor® RH40 and Labrasol® were used as surfactants for the screening of ME regions, Capmul® MCM L, Captex® 355, Imwitor® 408, Myglyol® 840 and Isopropyl myristate were the oil phases assayed; Transcutol® P, Polyethylene-glycol 400, glycerol, Propylene-glycol and ethanol the cosurfactants. Phe stability assay was carried out (20:4:20:56% and 20:4:35:41% (w/w); surfactant:oily phase:cosurfactant:water) for both surfactants; only one containing ethanol showed significant dismissing in its drug content. Solubility capacity for these selected formulations were also evaluated, an amount between 17 and 58 mg/mL of Phe could be loaded. At last, an optimized ME formulation with Cremophor® RH40 20%, Capmul® MCM L 4%, PEG 400 35% and sucralose 2% (w/w) was chosen in order to optimize taste-masking using an electronic tongue. Strawberry along with banana and tutti-frutti flavors plus mint flavor proved to be the best ones. Labrasol-based pre-concentrates were tested for (micro)emulsifying properties; all of them resulted to behave as SEDDS. In summary, a rationale experimental design conducted to an optimized ME for Phe oral pediatric administration which was able to load 5-fold times the currently used dose (4 mg/mL), with no sign of physical or chemical instability and with improved taste; SEDDS for capsule filling were also obtained. The biopharmaceutical advantages described for these dosage forms encourage furthering in vivo evaluation.

Lipid-based microtubes for topical delivery of amphotericin B.

The self-assembly process is a valuable tool for constructing nano and microstructures. Microtubes (MTs) self-assembled from amphiphiles are novel promising nanomaterials as they have easy self-assembly in aqueous solutions, reproducibility and biocompatibility. The incorporation of amphotericin B (AmB) into lipid microtubes formed from 12-hydroxystearic acid (12HSA) when mixed with ethanolamine in aqueous media was investigated. MTs of several concentrations of lipid material and AmB were prepared. The structure was characterized by phase-contrast microscopy, TEM and SEM. The type of interaction was analyzed by FTIR and DSC. Stability studies were carried out at room temperature and at 4 °C. Loading efficiency of the system was found to be much higher than the drug solubility in water. MTs with 1% of 12HSA and 1 mg/ml of AmB showed to be the most stable formulation. In vitro skin penetration assay showed a flux of 18.20±3.35 µg/cm(2). Amb-loaded MTs in vitro antifungal activity was evaluated and formulation showed similar results to that of AmB deoxycholate showing that AmB retained its antifungal activity in the MTs formulation.

Solubility of amphotericin B in water-lecithin-dispersions and lecithin-based submicron emulsions.

The aim of this work was to evaluate water-lecithin-dispersions (WLDs) as carriers for amphotericin B (AmB) and to compare the drug solubility in WLDs and O/W lecithin-based submicron emulsions (SMEs) in order to evaluate the influence of lecithin content on the dosage form solubilization of the active compound. WLDs and different SMEs with either 1.2 or 2.4% of lecithin were prepared. WLD with 2.4% lecithin show a 10-fold increase in solubilization of AmB compared with 1.2% lecithin WLD. SMEs with 1.2% lecithin show an increase of over 400 times in solubilization compared with WLD containing the same concentration of lecithin, whereas SMEs with 2.4% lecithin show an increase of over 40 times compared with the corresponding WLD. Drug solubilization in SMEs with 2.4% lecithin is not significantly greater than in those containing 1.2% lecithin. The content of surfactant Brij 97 ® had a significant influence on drug solubilization in SMEs (P < 0.05). Results indicate that indicate that SMEs are proper systems to solubilize AmB. It can be assumed that solubilization is due to the formulation microstructure and not to the separate components themselves.

Formulation Strategies, Characterization, and In Vitro Evaluation of Lecithin-Based Nanoparticles for siRNA Delivery.

The aim of the present work was to take advantage of lecithin's biocompatibility along with its physicochemical properties for the preparation of lecithin-based nanocarriers for small interfering RNA (siRNA) delivery. Water lecithin dispersions were prepared in different conditions, loaded with siRNA at different N/P ratios, and evaluated for loading capacity. The most appropriate ones were then assayed for cytotoxicity and characterized in terms of particle size distribution, zeta potential, and morphology. Results demonstrated that formulations prepared at pH 5.0 and 7.0 were able to load siRNA at broad N/P ratios, and cellular uptake assays showed an efficient delivery of oligos in MCF-7 human breast cancer cells; fluorescent-labeled dsRNA mainly located next to its target, near the nucleus of the cells. No signs of toxicity were observed for broad compositions of lecithin. The physicochemical characterization of the siRNA-loaded dispersions exhibited particles of nanometric sizes and pH-dependant shapes, which make them suitable for ex vivo and in vivo further evaluation.

An antibody recognizing the apical domain of human transferrin receptor 1 efficiently inhibits the entry of all new world hemorrhagic Fever arenaviruses.

Five New World (NW) arenaviruses cause human hemorrhagic fevers. Four of these arenaviruses are known to enter cells by binding human transferrin receptor 1 (hTfR1). Here we show that the fifth arenavirus, Chapare virus, similarly uses hTfR1. We also identify an anti-hTfR1 antibody, ch128.1, which efficiently inhibits entry mediated by the glycoproteins of all five viruses, as well as replication of infectious Junín virus. Our data indicate that all NW hemorrhagic fever arenaviruses utilize a common hTfR1 apical-domain epitope and suggest that therapeutic agents targeting this epitope, including ch128.1 itself, can be broadly effective in treating South American hemorrhagic fevers.

Visualization and quantification of cytotoxicity mediated by antibodies using imaging flow cytometry.

Conventional approaches for the detection of antibody dependent cell-mediated cytotoxicity (ADCC) activity rely on quantification of the release of traceable compounds from target cells or flow cytometry analysis of population-wide phenomena. We report a new method for the direct imaging and quantification of ADCC of cancer cells. The proposed method using imaging flow cytometry combines the statistical power of flow cytometry with the analytical advantages of cell imaging, providing a novel and more comprehensive perspective of effector/target cell interactions during ADCC events. With this method we can quantify and show in detail the morphological changes in target and effector cells, their apoptotic index, the physical interaction between effector and target cells, and a directional transfer of cytosolic contents from effector to target cells. As a model system we used the therapeutic anti-CD20 antibody rituximab to target CFSE labeled Ramos human Burkitt's lymphoma cells, to CMTPX-labeled human monocytic U-937 effector cells. We expect that similar studies using different effector and target cell populations may contribute to the pre-clinical evaluation of therapeutic antibodies and help to identify mechanisms that could be beneficial in the immunotherapy of cancer.

Preparation and characterization of iron-containing liposomes: their effect on soluble iron uptake by Caco-2 cells.

The aim of this work was to study the iron uptake of Caco-2 cells incubated with five different formulations of liposomes containing iron. The vesicles were also characterized before, during, and after in vitro digestion. Caco-2 cells were incubated with digested and nondigested liposomes, and soluble iron uptake was determined. Nondigested liposomes made with chitosan (CHI) or the cationic lipid, DC-Cholesterol (DC-CHOL), generated the highest iron uptake. However, these two formulations were highly unstable under in vitro digestion, resulting in nonmeasurable iron uptake. Digested conventional liposomes composed of soybean phosphatidylcholine (SPC), hydrogentated phosphatidylcholine (HSPC), or HSPC and cholesterol (CHOL) presented the highest iron-uptake values. These liposomal formulations protected iron from oxidation and improved iron uptake from intestinal cells, compared to an aqueous solution of ferrous sulphate.

Study of in vitro drug release and percutaneous absorption of fluconazole from topical dosage forms.

The present study aimed to evaluate different dosage forms, emulsions, emulgels, lipogels, and thickened microemulsion-based hydrogel, as fluconazole topical delivery systems with the purpose of determining a formulation with the capacity to deliver the whole active compound and maintain it within the skin so as to be considered a useful formulation either for topical mycosis treatment or as adjuvant in a combined therapy for Cutaneous Leishmaniasis. Propylene glycol and diethyleneglycol monoethyl ether were used for each dosage form as solvent for the drug and also as penetration enhancers. In vitro drug release after application of a clinically relevant dose of each formulation was evaluated and then microemulsions and lipogels were selected for the in vitro penetration and permeation study. Membranes of mixed cellulose esters and full-thickness pig ear skin were used for the in vitro studies. Candida albicans was used to test antifungal activity. A microemulsion containing diethyleneglycol monoethyl ether was found to be the optimum formulation as it was able to deliver the whole contained dose and enhance its skin penetration. Also this microemulsion showed the best performance in the antifungal activity test compared with the one containing propylene glycol. These results are according to previous reports of the advantages of microemulsions for topical administration and they are very promising for further clinical evaluation.

Asymmetric IgG antibodies induced by different immunotherapies in a murine model of allergy.

Specific immunotherapy (SIT) is the only potentially curative treatment for those allergic processes mediated by IgE. We compared the effects of different SITs in mice sensitised with ovalbumin (OVA) Al (OH)(3) : 1) OVA entrapped in particles of poly (D,L-lactic-co-glycolic acid) (PLGA-OVA), 2) Soluble OVA (OVA-sol) and 3) Polymerised OVA (OVA-pol). Serum levels of specific IgE, IgG1, IgG2a and asymmetric IgG, the cutaneous anaphylaxis test (PCA), and the IL-10, IFNgamma and IL-4 levels in culture supernatants of splenocytes challenged with OVA were assessed. Mice treated with PLGA-OVA had higher levels of asymmetric antibodies than non-desensitised mice; a low IgG1 and high IgG2a level was observed together with inhibitory effect in the PCA reaction that reversed in the absence of asymmetric IgG. IL-10 and IFNgamma levels were higher in supernatants from mice treated with PLGA-OVA and OVA-sol than those obtained from non-desensitised controls. Our results suggest that among the different SITs evaluated, PLGA-OVA is the one that best showed an increase in the asymmetric IgG molecules and an effective deviation of the immune response. Furthermore, the increase in the proportion of asymmetric antibodies would be of importance when designing new vaccination strategies for allergy.

Indinavir-loaded pH-sensitive microparticles for taste masking: toward extemporaneous pediatric anti-HIV/AIDS liquid formulations with improved patient compliance.

The aim of this work was to develop indinavir pediatric anti-HIV/AIDS formulations enabling convenient dose adjustment, ease of oral administration, and improved organoleptic properties by means of the generation of drug-loaded microparticles made of a polymer that is insoluble under intake conditions and dissolves fast in the stomach in order to completely release the active agent. Indinavir-loaded microparticles made of a pH-dependent polymeric excipient soluble at pH < 5, Eudragit E100, were prepared using a double emulsion solvent diffusion technique and the in vitro release profiles characterized. Finally, taste masking properties were evaluated in blind randomized sensory experiments by ten healthy human volunteers. The use of a w/o/o emulsion system resulted in indinavir loads around 90%. Thermal analysis of the microparticles by differential scanning calorimetry revealed that indinavir appeared mainly dispersed at the molecular level. Concentrations of residual organic solvents as determined by gas chromatography were below the upper limits specified by the European Pharmacopeia for pharmaceutical oral formulations. Then, the behavior of drug-containing microparticles in aqueous media at different pH values was assessed. While they selectively dissolved in gastric-like medium, in tap water (intake conditions), the matrix remained almost unchanged and efficiently prevented drug dissolution. Finally, sensoring taste tests performed by volunteers indicated that systems with indinavir loads approximately 15% displayed acceptable taste. This work explored the production of indinavir-containing microparticles based on a common pharmaceutical excipient as a means for the improvement of medicines of drugs involved in the treatment of HIV/AIDS. For systems containing about 15% drug, taste studies confirmed the acceptability of the formulation. In pediatric regimes, this composition would require an acceptable amount of formulation (0.7-1.5 g).

Gibbs energy of transfer processes for the antimicrobial agent Triclosan from water to some organic solvents at 25.0 °C

The thermodynamic function Gibbs energy for the dissolution processes of triclosan (TS) was calculated from solubility values obtained at 25.0 °C in organic solvents with different hydrogen-bonding capability. TS solubility was determined in ethanol, octanol, water-saturated octanol, isopropyl myristate, chloroform, and heptane. The excess Gibbs energy and the activity coefficients of the solute were also calculated. In addition, the corresponding Gibbs energies of the drug transfer process from water to the organic solvents under investigation were also calculated by means of previous reports. In all cases, this thermodynamic property comprised a negative value, indicating the preference of TS for all the organic media evaluated.

En este trabajo se presentan las energías de Gibbs para los procesos de disolución del triclosan (TS) en solventes orgánicos de diferente capacidad de formación de enlace de hidrógeno, las cuales fueron calculadas a partir de los valores de solubilidad a 25,0 °C. La solubilidad del TS se determinó en etanol, octanol, octanol saturado de agua, miristato de isopropilo, cloroformo, y heptano. Así mismo se calcularon las energías de Gibbs de exceso y los coeficientes de actividad del soluto en los mismos solventes. Adicionalmente, mediante el uso de valores previamente reportados en la literatura, se calcularon las energías de Gibbs de transferencia del TS desde el agua hasta los solventes orgánicos comprendidos en el estudio. En todos los casos, esta propiedad termodinámica fue negativa demostrando la preferencia del TS por los medios orgánicos evaluados.

Some considerations about the hydrophilic-lipophilic balance system.

The methods and results obtained by Griffin et al. in the determination of the hydrophilic-lipophilic balance (HLB) values of non-ionic surfactants and of required HLB values of oil mixtures are reviewed in the present work. HLB values published by Griffin were compared with those obtained by calculations from theoretic chemical formulas. Griffin HLB values of polyoxyethylene alkyl ethers, polyoxyethylene monoesters and propylene glycol monoesters coincide with those obtained from such theoretical chemical formulations. These results demonstrate that, for these surfactants, Griffin did not experimentally obtain their HLB values, but instead calculated them from theoretic formulae. For the calculation of the HLB values of glycerol monostearate, sorbitan fatty acid esters and polyoxyethylene sorbitan fatty acid esters, Griffin's assumptions were possibly based upon the mean saponification values of the ester and the acid of the fatty acid. It is concluded that the HLB values of non-ionic surfactants were not rigorously defined. Moreover, Griffin could not demonstrate the validity of the assumption that individual required HLB values can be added up to obtain the overall required HLB value of an oil mixture. The HLB and required HLB values published by Griffin should only be taken as approximate guidelines.

Release study of diclofenac from new carbomer gels.

Carbopol gels were prepared using a traditional polymer with mucoadhesive properties (974P). A new Carbomer derivative Ultrez 21 was also evaluated. Mineral oil, as occlusive ingredient, glycerol as humectant and ethanol were included in all the compositions. The feasibility of preparing these formulations with or without a bioadhesive polymer (Polycarbophil AA-1) and a second oil phase with enhancer activity (Miglyol 840) was evaluated. Further characterization including physical stability during a year was carried out. In vitro release behaviour of diclofenac sodium in Franz diffusion cell was evaluated with some selected formulations using an ethanol-water (50% w/w) solution as receptor medium. Addition of Polycarbophil AA-1 increased formulation viscosity and decreased drug release. These types of topical dosage forms could give sustained delivery of drug onto the skin, could tolerate the incorporation of an enhancer, a humectant and an occlusive phase, so they are interesting promises to improve skin absorption of nonsteroidal anti-inflammatory drugs and to prevent side effects associated.

Triclosan-loaded poloxamine micelles for enhanced topical antibacterial activity against biofilm.

Our research group is interested in the study of different technological approaches to treat hospital biofilm as a means to constrain nosocomial-acquired infections. The present work investigated the effect of the incorporation of the antibacterial agent triclosan (TS) into polymeric micelles of poloxamine T1107 (MW=15 kDa, 70 wt% PEO). The aggregation phenomenon was primarily investigated by means of Critical Micellar Concentration in a broad range of pH. Then, the effect of the polymer concentration on the micellar size was evaluated by Dynamic Light Scattering. Solubility levels increased up to 4 orders of magnitude. The drug inclusion affected the micellization, resulting in size increase and micellar fusion. This phenomenon was only apparent in TS-saturated systems. TS-loaded aggregates proved to be active in vitro against a broad spectrum of bacteria but more importantly, also against two representative clinical pathogens: methicilin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecalis (VREF). While the former was sensitive to even very low TS levels attainable in poloxamine-free aqueous media, the later was inhibited only when exposed to higher drug levels affordable exclusively using an inclusion system. These findings indicated the release of the drug from the reservoir. Finally, the activity of a TS-containing 5% poloxamine combination of pH 7.4 was assessed on biofilms of Staphylococcus epidermidis. Results showed a significant decrease (p<0.001) in the number of Colony-Formation Units when the biofilm was exposed to the TS/poloxamine as compared to the limited activity of the polymer-free TS control.

Comparison of the retention characteristics of different pseudostationary phases for microemulsion and micellar electrokinetic chromatography of betamethasone and derivatives.

Five electrokinetic chromatography systems were compared concerning retention behavior and lipophilicity. Comparison was based on capacity (retention) factors of some steroidal drugs, and on log P(OW) values derived by the aid of reference substances. In all systems the aqueous buffer consisted of phosphate (20 mM, pH 7.5). Two systems had micelles, three systems microdroplets as negatively charged pseudostationary phases. The micelles were formed by sodium dodecyl sulfate (SDS) and sodium cholate, respectively. One microemulsion consisted (as usual) from octane as oil, butanol as cosurfactant and SDS as charged tenside. Two microemulsions were made from biosurfactants (phosphatidylcholine, isopropylmyristate) to better simulate biopartitioning of the drugs. Even for noncharged analytes a change in migration sequence and thus in log P(OW) was observed for the systems consisting of the biosurfactants, compared to the others. For the former systems, log P(OW) derived from the capacity factors agree for all analytes with those obtained from calculation by computer software based on the structure of the drugs, and with experimental data directly obtained from octanol/water partitioning.

Viscosidad del semen humano: su relación con otras variables seminales / Viscocity of human semen: its relationship with other seminal variables

Se ha buscado: a) Establecer la validez matemática de la consistencia del semen como estimador de parámetros reológicos y b) evaluar el grado de compromiso de glándulas anexas y celularidad en el fenómeno de hiperviscosidad seminal. Las variables reológicas, viscosidad relativa (nr) y áreas de tixotropía (AT), determinadas en 247 sémenes, con viscosímetros capilares (Ostwald modificado (n:161) y rotacionales (Wells-Brookfield) (n:86), presentan diferencia altamente significativa (p<0,0001) entre las poblaciones de consistencia normal y aumentada. Las concentraciones de fructosa y ácido ascórbico (*mol/eyaculado) marcadores bioquímicos de vesícula seminal) y de ácido cítrico y fosfatasa (*mol/eyaculado y Ul/ml, respectivamente) (marcadores bioquímicos de próstata), muestran diferencia significativa entre los grupos de distinta consistencia (p<0,05). Las concentraciones de fructosa y ácido cítrico no se correlacionan con at en sémenes de consistencia normal, pero sí muestran correlación matemática en sémenes de consistencia aumentada. La relación Fructosa/Acido cítrico no presenta diferencia entre las poblaciones consideradas, ni se correlaciona con nr. No se halló correlación entre nr y número de espermatozoides/ml, ni entre nr y número de leucocitos y otras células/ml. Se concluye que: a) la consistencia seminal es un estimador cualitativo de nr y at; b) las glándulas anexas principales estarían comprometidas en el fenómeno de hiperviscosidad, no así el balance entre sus secreciones ni el número de elementos formes presentes