Physicochemical characterization and thermal behavior of hexosomes containing ketoconazole as potential topical antifungal delivery system.

OBJECTIVE: The main purpose of this article is to show the valuable characteristics that liotropic liquid crystal systems possess to be employed as new drug delivery systems. SIGNIFICANCE: Colloidal aqueous dispersions of lyotropic liquid crystal mesophases such as the identified as cubosomes and hexosomes, and so on, have received considerable attention due to their unique nanostructures and their thermodynamic properties, which provide the potential as a sustained drug release matrix. Additionally, their large surface area and similarity with the liquid crystal structures of intercellular lipids of stratum corneum enhances the interaction with the skin and mucous, increasing the potential for topical drug delivery efficiency of biopharmaceutical class II drugs as the antifungal ketoconazole. METHODS: This article presents the results in morphological characteristics, particle size, ζ potential, flow, thermal behavior and drug release studies of hexosomes containing ketoconazole (LHLC-K) obtained with glycerol monooleate, propylene glycol monolaurate, poloxamer, and water mixtures. RESULTS: This colloidal system exhibits a Newtonian-type flow and a hexagonal nanostructure with a median particle size of 107 ± 20 nm and ζ potential of +4.45 ± 0.50 mV. Through differential scanning calorimetry studies, the LHLC-K demonstrated physical and chemical stability for more than six months and mesophasic thermal reversibility between 10 and 50 °C. Finally, LHLC-K releases ketoconazole following a kinetics described by the first order model. CONCLUSIONS: Physicochemical properties of the hexosomes containing ketoconazole are important for topical mycosis treatment administration, conditions of storage, and for its incorporation into the formulation of semi-solid dosage forms.

Diagnóstico y tratamiento de la gota / Gout: Diagnosis and treatment

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Organic cocoa extract -loaded surfactant-based systems intended to skin bioadhesion

ABSTRACT This study was to develop, characterize, and evaluate the physical-chemical stability, in vitro antioxidant activity and in vitro safety profile of liquid crystalline systems (LCS) and microemulsions (MEs) with and without organic cocoa (OC) extract. LCS stabilized by surfactant polyoxyethylene 20 cetyl ether, containing water and oleic acid were studied. LCS and MEs were characterized using polarized light microscopy, small angle X-ray scattering, rheology and in vitro bioadhesion, and were evaluated for a period of 30 days by visual aspects, centrifuge test, pH value and relative density. PLM and SAXS assays showed the presence of domains of MEs, cubic and hexagonal mesophasephases, varying the proportions of the components of the formulations; where in the addition of the extract did not change rheological behavior of the formulations. All of the formulations were stable in the period analyzed and presented higher bioadhesive strength. In vitro antioxidant activity suggests that LCS and MEs presented a high capacity to maintain the antioxidant activity of OC extract. The results showed that the incorporation of OC in LCS improved the safety profile, according to cytotoxicity assays of systems may be a promising platform to OC extract for topical application for the potential treatment of skin disorders.

A Fast and Sensitive Method for the Detection of Leuprolide Acetate: A High-Throughput Approach for the In Vitro Evaluation of Liquid Crystal Formulations.

The suitability of using fluorescence spectroscopy to rapidly assay drug release by quantifying the time-dependent increase in total intrinsic protein fluorescence was assessed. Leuprolide acetate, a synthetic nonapeptide analogue of gonadotropin-releasing hormone (GnRH or LHRH), is the active pharmaceutical ingredient used to treat a wide range of sex hormone-related disorders, including advanced prostatic cancer, endometriosis, and precocious puberty. During the in vitro evaluation of drug delivery technologies for leuprolide acetate, one of the most time-consuming steps is the detection and accurate quantification of leuprolide release from formulation candidates. Thus far, the dominant means for leuprolide detection involves conventional multistep high-performance liquid chromatography (HPLC) methods, requiring sampling, dilutions, sample filtration, and chromatography, which can take up to 40 min for each sample. With the increasing demand for assay adaptation to high-throughput format, here we sought to exploit fluorescence spectroscopy as a tool to develop a novel method to rapidly assay the in vitro release of leuprolide acetate. By utilizing the intrinsic fluorescence of the tryptophan (Trp) and tyrosine (Tyr) amino acid residues present in the leuprolide nonapeptide, the in vitro release from liquid crystal formulations was accurately quantified as a function of fluorescence intensity. Here, we demonstrate that assaying leuprolide release using intrinsic protein fluorescence in a 96-well format requiring volumes as low as 100 µL is a cost-effective, rapid, and highly sensitive alternative to conventional HPLC methods. Furthermore, the high signal-to-noise ratios and robust Z'-factors of >0.8 indicate high sensitivity, precision, and feasibility for miniaturization, high-throughput format adaptation, and automation.

Development of nanotechnology-based drug delivery systems with olive vegetable oil for cutaneous application

ABSTRACT Liquid-Crystalline Systems represent active compounds delivery systems that may be able to overcome the physical barrier of the skin, especially represented by the stratum corneum. To obtain these systems, aqueous and oily components are used with surfactants. Of the different association structures in such systems, the liquid-crystalline offer numerous advantages to a topical product. This manuscript presents the development of liquid-crystalline systems consisting, in which the oil component is olive oil, its rheological characterizations, and the location of liquid crystals in its phase map. Cytotoxic effects were evaluated using J-774 mouse macrophages as the cellular model. A phase diagram to mix three components with different proportions was constructed. Two liquid crystalline areas were found with olive oil in different regions in the ternary diagram with two nonionic surfactants, called SLC1 (S1) and SLC2 (S2). These systems showed lamellar liquid crystals that remained stable during the entire analysis time. The systems were also characterized rheologically with pseudoplastic behavior without thixotropy. The texture and bioadhesion assays showed that formulations were similar statistically (p < 0.05), indicating that the increased amount of water in S2 did not interfere with the bioadhesive properties of the systems. In vitro cytotoxic assays showed that formulations did not present cytotoxicity. Olive oil-based systems may be a promising platform for skin delivery of drugs.

RESUMO Os cristais líquidos representam um sistema de liberação de substâncias ativas capazes de vencer a barreira cutânea, representada especialmente pelo estrato córneo. Água, óleo e tensoativos são misturados para se obter esses sistemas. Diferentes estruturas podem ser formadas nesses sistemas, as quais oferecem muitas vantagens para os produtos de uso tópico. Esse trabalho visou ao desenvolvimento de sistemas líquido-cristalinos preparados com óleo de oliva, sua caracterização reológica e a identificação das fases cristalinas no diagrama ternário. Efeitos citotóxicos foram avaliados usando células de rato como modelo celular. Construiu-se um diagrama de fases que mistura três componentes em diferentes proporções. Duas áreas de cristal líquido, denominadas SLC1 (S1) e SLC2 (S2), foram encontradas com óleo de oliva em diferentes regiões no diagrama ternário preparado com dois diferentes tensoativos não-iônicos. Esses sistemas mostraram fase cristalina lamelar, que permaneceu estável durante o tempo estudado. Os sistemas foram também caracterizados reologicamente e apresentaram comportamento pseudoplástico com tixotropia. Os ensaios de textura e bioadesão mostraram que as formulações foram similares (p < 0.05), indicando que o aumento da quantidade de água em S2 não interferiu nas propriedades bioadesivas dos sistemas. Os ensaios de citotoxicidade mostraram que as formulações não foram citotóxicas. Sistemas à base de óleo de oliva são interessantes para a liberação de fármacos na pele.

Materials recovery from waste liquid crystal displays: A focus on indium.

In the present work the recovery of indium and of the polarizing film from waste liquid crystal displays was experimentally investigated in the laboratory. First of all, the polarizing film was removed by employing a number of different techniques, including thermal and chemical treatments. Leaching of indium was then performed with HCl 6N, which allowed solubilisation of approximately 90% In (i.e. 260 mg In per kg of glass) at room temperature, without shredding. Indium recovery from the aqueous phase was then investigated through solvent extraction with polyethylene glycol (PEG)-based aqueous biphasic systems. Indium extraction tests through the PEG-ammonium sulphate-water system were conducted as a function of PEG concentration, salt concentration and molecular weight of PEG, using 1,10 phenanthroline as a ligand. The experimental results demonstrated that indium partitioning between the bottom (salt-rich) and the top (PEG-rich) phase is quite independent on the composition of the system, since 80-95% indium is extracted in the bottom phase and 5-20% in the top phase; it was also found that when PEG concentration is increased, the ratio between the bottom and the upper phase volumes decreases, resulting in an increase of indium concentration in the bottom phase (at [PEG]=25% w/w, indium concentration in the bottom phase is ∼30% higher than the initial concentration before the extraction).

An evaluation of the potential yield of indium recycled from end-of-life LCDs: A case study in China.

With the advances in electronics and information technology, China has gradually become the largest consumer of household appliances (HAs). Increasingly, end-of-life (EOL) HAs are generated in China. EOL recycling is a promising strategy to reduce dependence on virgin production, and indium is one of the recycled substances. The potential yield of indium recycling has not been systematically evaluated in China thus far. This paper estimates the potential yield of recycled indium from waste liquid crystal displays (LCDs) in China during the period from 2015 to 2030. The quantities of indium that will be used to produce LCDs are also predicted. The estimates focus on the following three key LCD waste sources: LCD TVs, desktop computers and portable computers. The results show that the demand for indium will be increasing in the near future. It is expected that 350 tonnes of indium will be needed to produce LCDs in China in 2035. The indium recycled from EOL LCDs, however, is much less than the demand and only accounts for approximately 48% of the indium demand. The sustainable index of indium is always less than 0.5. Therefore, future indium recycling efforts should focus on the development of recycling technology and the improvement of the relevant policy.

Leaching capacity of metals-metalloids and recovery of valuable materials from waste LCDs.

The purpose of Directive 2012/19/EU which is related to WEEE (Waste Electrical and Electronic Equipment), also known as "e-waste", is to contribute to their sustainable production and consumption that would most possibly be achieved by their recovery, recycling and reuse. Under this perspective, the present study focused on the recovery of valuable materials, metals and metalloids from LCDs (Liquid Crystal Displays). Indium (In), arsenic (As) and stibium (Sb) were selected to be examined for their Leaching Capacity (R) from waste LCDs. Indium was selected mainly due to its rarity and preciousness, As due to its high toxicity and wide use in LCDs and Sb due to its recent application as arsenic's replacement to improve the optimal clarity of a LCD screen. The experimental procedure included disassembly of screens along with removal and recovery of polarizers via thermal shock, cutting, pulverization and digestion of the shredded material and finally leaching evaluation of the aforementioned elements. Leaching tests were conducted under various temperatures, using various solid:liquid (S/L) ratios and solvents (acid mixtures), to determine the optimal conditions for obtaining the maximum leaching capacities. The examined elements exhibited different leaching behaviors, mainly due to the considerable diversity in their inherent characteristic properties. Indium demonstrated the highest recovery percentages (approximately 60%), while the recovery of As and Sb was unsuccessful, obtaining poor leaching percentages (0.16% and 0.5%, respectively).

Recovery of indium from LCD screens of discarded cell phones.

Advances in technological development have resulted in high consumption of electrical and electronic equipment (EEE), amongst which are cell phones, which have LCD (liquid crystal display) screens as one of their main components. These multilayer screens are composed of different materials, some with high added value, as in the case of the indium present in the form of indium tin oxide (ITO, or tin-doped indium oxide). Indium is a precious metal with relatively limited natural reserves (Dodbida et al., 2012), so it can be profitable to recover it from discarded LCD screens. The objective of this study was to develop a complete process for recovering indium from LCD screens. Firstly, the screens were manually removed from cell phones. In the next step, a pretreatment was developed for removal of the polarizing film from the glass of the LCD panels, because the adherence of this film to the glass complicated the comminution process. The choice of mill was based on tests using different equipment (knife mill, hammer mill, and ball mill) to disintegrate the LCD screens, either before or after removal of the polarizing film. In the leaching process, it was possible to extract 96.4 wt.% of the indium under the following conditions: 1.0M H2SO4, 1:50 solid/liquid ratio, 90°C, 1h, and stirring at 500 rpm. The results showed that the best experimental conditions enabled extraction of 613 mg of indium/kg of LCD powder. Finally, precipitation of the indium with NH4OH was tested at different pH values, and 99.8 wt.% precipitation was achieved at pH 7.4.

Reposición de volumen: ¿cristaloides o coloides? / Restoring blood volume: crystalloids or colloids?

El uso de coloides y cristaloides en la reposición de volumen es una estrategia habitual en la estabilización clínica de los paciente críticos. En general, los coloides se han mostrado más potentes y rápidos que los cristaloides en la reposición de volemia y estabilización hemodinámica, pero varios estudios han evidenciado mayor riesgo de insuficiencia renal aguda y necesidad de terapias de sustitución renal. Los resultados dispares de diferentes estudios respecto a la supervivencia o el daño renal podrían explicarse por la selección de la población tratada y la velocidad de reposición de volemia. En general, los pacientes tratados con coloides con datos hemodinámicos de hipovolemia y tratados con bajos ritmos de reposición presentan resultados similares a los de los tratados con cristaloides. Es importante destacar que la expansión de volemia es una ayuda en el manejo del paciente crítico, pero no es el tratamiento fundamental etiológico del shock. Finalmente, es imprescindible un control hemodinámico estricto del efecto de la reposición de volumen, con parámetros en tiempo real y objetivos bien definidos (AU)

The use of colloid and crystalloid fluids for the restoration of blood volume is a common clinical strategy for stabilizing patients receiving critical care. In general, colloids have been found to be more effective and faster-acting than crystalloids for volume restoration and hemodynamic stabilization, but several studies have shown that they are also associated with a greater risk of acute renal failure and the need for renal replacement therapy. The variation in survival and kidney injury rates observed between different studies might be explained by differences in the patient population selected or the speed of blood volume restoration. In general, patients with hemodynamic evidence of hypovolemia who receive colloids at a low fluid replacement rate achieve similar results to those treated with crystalloids. It is important to note that, although volume expansion is helpful in the management of critically ill patients, it does not resolve the etiological factors underlying shock. Finally, strict hemodynamic control of the effects of volume restoration is essential and should be based on real-time parameters and clearly defined objectives (AU)

Los cocristales farmacéuticos: conceptos generales / Pharmaceutical Cocrystals: General concepts

Los cocristales farmacéuticos surgen como una posibilidad para mejorar las propiedades biofarmacéuticas y farmacotécnicas de un IFA (Ingrediente Farmacéutico Activo). Los cocristales farmacéuticos son sólidos cristalinos constituidos por un IFA y un formador, los cuales se encuentran en la misma celda cristalina. La búsqueda de nuevos cocristales farmacéuticos es competencia de la química supramolecular, ya que el IFA y el formador se mantienen juntos mediante interacciones no covalentes. Existen métodos en solución y en sólidos para la formación de cocristales. Además, este campo ofrece una posibilidad de desarrollo intelectual debido a la posibilidad de patentar los productos, considerando los parámetros regulatorios. Este trabajo presenta los principales conceptos que se consideran para el estudio de estos sólidos farmacéuticos

Pharmaceutical co-crystals emerge as a possibility to improve the biopharmaceutical properties and pharmacotechnical of an Active Pharmaceutical Ingredient (API). Theco-crystalsare crystalline solids composed of an API and a former, which are located in the same crystal cell. The search for new pharmaceutical co-crystals is the responsibility of supramolecular chemistry, since the formerand the API are held together by non-covalent interactions. Solution and solid state methods are employed for the formation of cocrystals. In addition, this field offers a possibility of intellectual development due to the patentability of products, without neglecting the regulatory aspects. This work presents the main concepts considered for the study of these pharmaceutical solids

Liquid-crystal science from 1888 to 1922: building a revolution.

The saga of liquid crystals started with their discovery in 1888 by the botanist Friedrich Reinitzer, who unexpectedly observed "two melting points" for crystals extracted from the root of a carrot. At the end of the nineteenth century, most scientists did not believe in the existence of "liquid crystals" as promoted by the crystallographer Otto Lehmann. The controversies were very vivid; to the point that the recognition of mesomorphic states of matter by the scientific community required more than two decades. In the end, liquid crystals have changed our vision of matter by shattering the three-state paradigm. Since the mid-1970s, liquid crystals have revolutionized the worldwide information-display industry and now play a host of key roles in various technologies.

Determination of surface nematic liquid crystal anchoring strength using nano-scale surface grooves.

Based on several nano-scale groove models, we propose a new technique to simultaneously determine the azimuthal and polar surface anchoring strengths of nematic liquid crystal (LC). The optical analysis of LCs on a grooved surface made by nanoimprinting lithography was performed on special alignment material, using a typical rubbing process. In our approach, using a polarizing microscope, we can determine the LC alignment exactly as it is in a parallel state, rather than a twisted state. This simple proposed method gives an accurate value of the surface LC anchoring of various surfaces, as well as simultaneously measuring the azimuthal and polar anchoring energy.

Descripción de una cristaluria por amoxicilina / Description of an amoxicillin crystalluria

Se estudia la orina de una paciente tratada con amoxicilina por neumonía adquirida en la comunidad. Se observa el depósito de los cristales característicos (gavillas de trigo) de este antibiótico con un sistema óptico digital y se identifican por cromatografía líquida de intercambio catiónico (AU)

The urine of a patient treated with amoxicillin for community-acquired pneumonia was studied. Using an automated digital microscope, it was possible to appreciate the characteristic wheat-sheaf-like crystals of this antibiotic, to subsequently identify them by cation-exchange liquid chromatography (AU)

Signal intensities in ¹H-¹³C CP and INEPT MAS NMR of liquid crystals.

Spectral editing with CP and INEPT in (13)C MAS NMR enables identification of rigid and mobile molecular segments in concentrated assemblies of surfactants, lipids, and/or proteins. In order to get stricter definitions of the terms "rigid" and "mobile", as well as resolving some ambiguities in the interpretation of CP and INEPT data, we have developed a theoretical model for calculating the CP and INEPT intensities as a function of rotational correlation time τc and C-H bond order parameter SCH, taking the effects of MAS into account. According to the model, the range of τc can at typical experimental settings (5kHz MAS, 1ms ramped CP at 80-100kHz B1 fields) be divided into four regimes: fast (τc<1ns), fast-intermediate (τc≈0.1µs), intermediate (τc≈1µs), and slow (τc>0.1ms). In the fast regime, the CP and INEPT intensities are independent of τc, but strongly dependent on |SCH|, with a cross-over from dominating INEPT to dominating CP at |SCH|>0.1. In the intermediate regime, neither CP nor INEPT yield signal on account of fast T1ρ and T2 relaxation. In both the fast-intermediate and slow regimes, there is exclusively CP signal. The theoretical predictions are tested by experiments on the glass-forming surfactant n-octyl-ß-d-maltoside, for which τc can be varied continuously in the nano- to millisecond range by changing the temperature and the hydration level. The atomistic details of the surfactant dynamics are investigated with MD simulations. Based on the theoretical model, we propose a procedure for calculating CP and INEPT intensities directly from MD simulation trajectories. While MD shows that there is a continuous gradient of τc from the surfactant polar headgroup towards the methyl group at the end of the hydrocarbon chain, analysis of the experimental CP and INEPT data indicates that this gradient gets steeper with decreasing temperature and hydration level, eventually spanning four orders of magnitude at completely dry conditions.

Nonlinear photoluminescence imaging of isotropic and liquid crystalline dispersions of graphene oxide.

We report a visible-range nonlinear photoluminescence (PL) from graphene oxide (GO) flakes excited by near-infrared femtosecond laser light. PL intensity has nonlinear dependence on the laser power, implying a multiphoton excitation process, and also strongly depends on a linear polarization orientation of excitation light, being at maximum when it is parallel to flakes. We show that PL can be used for a fully three-dimensional label-free imaging of isotropic, nematic, and lamellar liquid crystalline dispersions of GO flakes in water. This nonlinear PL is of interest for applications in direct label-free imaging of composite materials and study of orientational ordering in mesomorphic phases formed by these flakes, as well as in biomedical and sensing applications utilizing GO.

Total internal reflection Raman spectroscopy.

Total internal reflection (TIR) Raman spectroscopy is an experimentally straightforward, surface-sensitive technique for obtaining chemically specific spectroscopic information from a region within approximately 100-200 nm of a surface. While TIR Raman spectroscopy has long been overshadowed by surface-enhanced Raman scattering, with modern instrumentation TIR Raman spectra can be acquired from sub-nm thick films in only a few seconds. In this review, we describe the physical basis of TIR Raman spectroscopy and illustrate the performance of the technique in the diverse fields of surfactant adsorption, liquid crystals, lubrication, polymer films and biological interfaces, including both macroscopic structures such as the surfaces of leaves, and microscopic structures such as lipid bilayers. Progress, and challenges, in using TIR Raman to obtain depth profiles with sub-diffraction resolution are described.

Graphene chiral liquid crystals and macroscopic assembled fibres.

Chirality and liquid crystals are both widely expressed in nature and biology. Helical assembly of mesophasic molecules and colloids may produce intriguing chiral liquid crystals. To date, chiral liquid crystals of 2D colloids have not been explored. As a typical 2D colloid, graphene is now receiving unprecedented attention. However, making macroscopic graphene fibres is hindered by the poor dispersibility of graphene and by the lack of an assembly method. Here we report that soluble, chemically oxidized graphene or graphene oxide sheets can form chiral liquid crystals in a twist-grain-boundary phase-like model with simultaneous lamellar ordering and long-range helical frustrations. Aqueous graphene oxide liquid crystals were continuously spun into metres of macroscopic graphene oxide fibres; subsequent chemical reduction gave the first macroscopic neat graphene fibres with high conductivity and good mechanical performance. The flexible, strong graphene fibres were knitted into designed patterns and into directionally conductive textiles.

Triazole-modified triphenylene derivative: self-assembly and sensing applications.

Triphenylene-based discotic liquid crystal 3 bearing 1,2,3-triazole groups has been synthesized using "click" chemistry. Discotic mesogen 3 has good thermal stability, and incorporation of triazole groups results in stabilization of columnar mesophases down to room temperature and formation of organogels in cyclohexane and mixed solvents such as hexane and dichloromethane (4:1 v/v). Characterization of the organogel of 3 in cyclohexane revealed a porous network. However, presence of Cd(2+) ions in solution obstructed the self-assembly of this derivative due to preferred interactions between Cd(2+) ions and triphenylene units over π-π interactions among triphenylene groups. Further, strong emission of derivative 3 in its nonaggregated form makes it a promising fluorescence sensory material for nitroaromatic compounds.

Research and assessment of safety distance of TV electromagnetic fields.

The evaluation covers the strengths of electric field and magnetic flux density measured in frequency ranges of 5 Hz-2 kHz and 2-400 kHz of selected TV sets. The dependence of the electromagnetic field on the distance is addressed with reference to ergonomics and safety. Ten TV sets (5 tube and 5 LCD) were measured. There were 16 measurements for each one. The aim was to evaluate electric field and magnetic flux density versus the distance from the tested device with regard to exposure levels. In addition, the distance and the strengths of electric field and magnetic flux density emitted by tube and LCD TVs were compared. The results are presented in charts.