Co-encapsulation of drugs directed at commonly associated diseases provides a convenient means for administration, especially if transdermally delivered.
In this work, a comprehensive study for the ...co-encapsulation of drugs with a differential lipophilicity, olanzapine and simvastatin, and their transdermal delivery in a formulation containing nanostructured lipid carriers (NLC) is presented. Focus is given to the evaluation of a strategy in which NLC and chemical permeation enhancers are combined. It comprises in vitro, in silico and cellular viability approaches. The optimization and rationalization of the systems are carried out using a two-step factorial design. It is shown that the external medium in the NLC dispersion strongly influences permeation. It is also seen that the use of NLC determines a synergistic effect with selected permeation enhancers, thus promoting marked flux enhancement ratios (48 and 21, respectively for olanzapine and simvastatin) relative to the drugs in solution. The developed formulations can be considered non-irritant. A correlation between enhancer positioning in a lipid bilayer, partially governed by a H-bonding phenomenon, and enhancement effect is suggested from molecular dynamics studies and experimental observations.
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Abstract Lung cancer remains a leading cause of death due to the low efficacy of chemotherapy, mainly related to the administration route used. Therefore, alternative administration routes are ...needed. Paclitaxel (PTX) is an insoluble anticancer drug active against solid tumors, such as those found in lung cancer, that has stimulated an intense research effort over recent years. Solid lipid nanoparticles (SLNs) are potential carriers for poorly soluble drugs, being biodegradable systems that served as alternatives to the usual colloidal carriers. That system was used to deliver PTX to the lungs and seem to fulfill the requirements for an optimum particulate carrier. Furthermore, PTX-loaded SLN pulmonary administration provided a target administration, which is expected to avoid high concentration of the drug at nontarget tissues, reducing toxicity, and increasing the drug's therapeutic index. The rationale of this study was to deliver a colloidal system to the lung lymphatics through a pulmonary route for cancer therapy. From the Clinical Editor Paclitaxel-loaded solid lipid nanoparticles were used to target tumors in a murine lung cancer model enabling high PTX concentration in the target with reduced systemic toxicity and increased therapeutic index.
Using the k-means cluster analysis algorithm, we carry out an unsupervised classification of all galaxy spectra in the seventh and final Sloan Digital Sky Survey data release (SDSS/DR7). Except for ...the shift to rest-frame wavelengths and the normalization to the g-band flux, no manipulation is applied to the original spectra. The algorithm guarantees that galaxies with similar spectra belong to the same class. We find that 99% of the galaxies can be assigned to only 17 major classes, with 11 additional minor classes including the remaining 1%. The classification is not unique since many galaxies appear in between classes; however, our rendering of the algorithm overcomes this weakness with a tool to identify borderline galaxies. Each class is characterized by a template spectrum, which is the average of all the spectra of the galaxies in the class. These low-noise template spectra vary smoothly and continuously along a sequence labeled from 0 to 27, from the reddest class to the bluest class. Our Automatic Spectroscopic K-means-based (ASK) classification separates galaxies in colors, with classes characteristic of the red sequence, the blue cloud, as well as the green valley. When red sequence galaxies and green valley galaxies present emission lines, they are characteristic of active galactic nucleus activity. Blue galaxy classes have emission lines corresponding to star formation regions. We find the expected correlation between spectroscopic class and Hubble type, but this relationship exhibits a high intrinsic scatter. Several potential uses of the ASK classification are identified and sketched, including fast determination of physical properties by interpolation, classes as templates in redshift determinations, and target selection in follow-up works (we find classes of Seyfert galaxies, green valley galaxies, as well as a significant number of outliers). The ASK classification is publicly accessible through various Web sites.
Poly(methyl methacrylate) (PMMA) is one of the most widely explored biomedical materials because of its biocompatibility, and recent publications have shown an increasing interest in its applications ...as a drug carrier. PMMA-based particulate carriers (PMMAP) can be prepared either by polymerization methods or from pre-formed polymer-based techniques. Potential biomedical application of these particles includes their use as adjuvant for vaccines and carrier of many drugs as antibiotics and antioxidants via different routes of administration. Release of drugs from PMMAP occurs typically in a biphasic way with an incomplete drug release. To improve release profiles, recent strategies are focusing on increasing polymer hydrophilicity by synthesizing functionalized PMMA microspheres or by formulating PMMA composites with hydrophilic polymers. This review examines the current status of preparation techniques, drug release kinetics, biomedical applications and toxicity of these nano/micro PMMA-based particulate carriers.
Although mental disorders are significant predictors of educational attainment throughout the entire educational career, most research on mental disorders among students has focused on the primary ...and secondary school years.
The World Health Organization World Mental Health Surveys were used to examine the associations of mental disorders with college entry and attrition by comparing college students (n = 1572) and non-students in the same age range (18-22 years; n = 4178), including non-students who recently left college without graduating (n = 702) based on surveys in 21 countries (four low/lower-middle income, five upper-middle-income, one lower-middle or upper-middle at the times of two different surveys, and 11 high income). Lifetime and 12-month prevalence and age-of-onset of DSM-IV anxiety, mood, behavioral and substance disorders were assessed with the Composite International Diagnostic Interview (CIDI).
One-fifth (20.3%) of college students had 12-month DSM-IV/CIDI disorders; 83.1% of these cases had pre-matriculation onsets. Disorders with pre-matriculation onsets were more important than those with post-matriculation onsets in predicting subsequent college attrition, with substance disorders and, among women, major depression the most important such disorders. Only 16.4% of students with 12-month disorders received any 12-month healthcare treatment for their mental disorders.
Mental disorders are common among college students, have onsets that mostly occur prior to college entry, in the case of pre-matriculation disorders are associated with college attrition, and are typically untreated. Detection and effective treatment of these disorders early in the college career might reduce attrition and improve educational and psychosocial functioning.
Renewable biofuels are increasingly important in the Brazilian energy matrix. In 2010, the country became the second world producer of biodiesel with a production of 2.4 million of m3 in that year, ...only behind Germany. In 2011, both the United States and Argentina increased production and now Brazil is the fourth world producer of biodiesel. The Brazilian biodiesel production federal program has been designed so that small family farmers, as well as large agribusiness operations, are encouraged to produce vegetable oil crops for biodiesel production. Brazil is the second largest world producer of soybeans, currently the main feedstock used for biodiesel production in the country. Due to the increasing demand for biodiesel and low oil productivity from soybean, Brazil is searching for alternative oilseed crops from which biodiesel can be produced. In this review, the current scenario for biodiesel production in Brazil is discussed, as well as vegetable oil crops that are being considered as potential biodiesel feedstocks in addition to soybeans. Brazil's biodiesel industry is currently operating only at 47% of its capacity. Therefore, it is expected that biodiesel production in Brazil will further increase. Due to the size of the country's bioethanol and biodiesel industries, Brazil can already be considered one of the world powers in sustainable biofuel production, an strategic area of the world's emerging bio-based economy.
The aim of the present study was to develop novel Mycobacterium bovis bacille Calmette-Guérin (BCG)-loaded polymeric microparticles with optimized particle surface characteristics and ...biocompatibility, so that whole live attenuated bacteria could be further used for pre-exposure vaccination against Mycobacterium tuberculosis by the intranasal route. BCG was encapsulated in chitosan and alginate microparticles through three different polyionic complexation methods by high speed stirring. For comparison purposes, similar formulations were prepared with high shear homogenization and sonication. Additional optimization studies were conducted with polymers of different quality specifications in a wide range of pH values, and with three different cryoprotectors. Particle morphology, size distribution, encapsulation efficiency, surface charge, physicochemical properties and biocompatibility were assessed. Particles exhibited a micrometer size and a spherical morphology. Chitosan addition to BCG shifted the bacilli surface charge from negative zeta potential values to strongly positive ones. Chitosan of low molecular weight produced particle suspensions of lower size distribution and higher stability, allowing efficient BCG encapsulation and biocompatibility. Particle formulation consistency was improved when the availability of functional groups from alginate and chitosan was close to stoichiometric proportion. Thus, the herein described microparticulate system constitutes a promising strategy to deliver BCG vaccine by the intranasal route.
This work presents a generalization of the functions used in Fraeijs de Veubeke's quadrilateral (FVQ) element and in Hsieh, Clough and Tocher's (HCT) triangle, allowing for an arbitrary degree of the ...approximation, d$$ d $$, and for arbitrary order of continuity, r$$ r $$. These functions can be used to define finite elements that lead by direct assembly to Cr$$ {C}^r $$ approximations. Their determination for each element is procedural, generalizing the reasoning used by Zienkiewicz to explain the FVQ element. The completeness of each basis is confirmed by comparing its dimension with that of a broken basis, defined primitive element wise, upon which the continuity constraints are successively imposed. The order of continuity at the vertices that is required to enable the independent definition of the normal derivatives at the sides is confirmed numerically. The corresponding interpolation functions are symbolically derived using Mathematica, and simple matlab codes using the data thus obtained are made available, to illustrate their application.
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