1,720,963 research outputs found
Nanostructured lipid-based drug delivery systems for poorly water-soluble drugs administration
No full textLa metà del XX secolo ha segnato l'inizio di quella che è stata definita la "età dell'oro" nella scoperta di farmaci. I progressi nella sintesi automatizzata e nell'uso del high-throughput screening (HTS), della genomica e della chimica combinatoria hanno portato a un incremento Costante del numero di potenziali molecole ad elevato valore farmacologico. Contemporaneamente, è ampiamente riconosciuto che, a seguito dell'introduzione di HTS e della chimica combinatoria, le proprietà delle new molecular entities (NME) si sono orientate verso un maggiore peso molecolare e una crescente lipofilia. Questo cambiamento ha comportato, di conseguenza, l'introduzione di farmaci più scarsamente solubili in acqua nella pipeline farmaceutica. Tuttavia, diversi problemi legati alla somministrazione di farmaci scarsamente solubili in acqua ostacolano il loro impiego terapeutico. A tal riguardo, la presente tesi di dottorato si propone di esplorare e mettere in evidenza il potenziale di diversi sistemi lipidici nanostrutturati (NLDDS) nella veicolazione di principi attivi scarsamente solubili in acqua, superando le limitazioni ad esse correlate. Nel dettaglio, vengono presentati una serie di casi di studio, in cui viene ampiamente esaminato e discusso il potenziale di specifici NLDDS nel solubilizzare, caricare e somministrare quattro differenti principi attivi scarsamente solubili. Sono stati studiati gel ethosomiali e transethosomiali come potenziali sistemi di somministrazione per il dimetilfumarato. Nanoparticelle ibride lipidiche/polimeriche decorate con ligandi recettore/specifici sono state progettate e studiate come potenziali nanocarrier in grado di superare i problemi di solubilità legati alla somministrazione orale di Urolitina A. Lo sviluppo e la valutazione di liposomi caricati con Nutlin-3a per il trattamento delle malattie vitreoretiniche proliferative sono descritti, e infine, i in situ forming gels sono stati proposti come potenziali sistemi di somministrazione a lunga durata per la co-somministrazione sottocutanea di curcumina e piperina. Per ciascuno di questi studi, i sistemi di somministrazione di farmaci esaminati sono stati approfonditamente studiati e caratterizzati. Inoltre, sono stati condotti studi tecnologici e biologici in vitro, insieme a esperimenti ex vivo o in vivo, per valutare l'efficacia terapeutica delle formulazioni. In generale, i risultati della ricerca presentati in questa tesi evidenziano i vantaggi dell'impiego degli NLDDS rispetto a strategie più convenzionali per superare le problematiche di solubilità dei farmaci. Inoltre, i risultati sottolineano l'importanza di un approfondito e dettagliato processo di caratterizzazione e studio del sistema nella progettazione di nuovi nanosistemi ad alta specificità, madellato sulle proprietà del farmaco, la via di somministrazione selezionata e le specificità del bersaglio terapeutico.The mid-20th century marked the onset of what has been termed the "golden age" of drug discovery. The advances in automated synthesis and the use of high-throughput screening (HTS), genomics and combinatorial chemistry have led to a steady increase in the number of potential drug candidates. At the same time, it is widely recognized that following the introduction of HTS and combinatorial chemistry, the properties of new molecular entities (NMEs) have shifted towards higher molecular weight and increasing lipophilicity. This shift has consequently resulted in the introduction of more poorly water-soluble drugs into the pharmaceutical pipeline. Nevertheless, several major issues related to the administration of poorly water-soluble drugs hamper their therapeutic employment. In this regard, the present doctoral thesis aims to explore and highlight the potential of different nanostructured lipid drug delivery systems (NLDDS) for the administration of poorly water-soluble active compounds, overcoming their solubility-related limitations. In detail, a series of case studies are presented, in which the potential of specific NLDDS to solubilize, load, and deliver five different poorly soluble active compounds is extensively examined and discussed. Ethosomal and transethosomal gels have been investigated as potential delivery systems for dimethyl fumarate. Highly specialized ligand-decorated lipid/polymer hybrid nanoparticles with specificity toward the transferrin receptor have been designed and studied as potential nanocarriers capable of overcoming the solubility issues related to the oral administration of Urolithin A. The development and evaluation of Nutlin-3a-loaded liposomes for the treatment of proliferative vitreoretinal diseases are described, and finally, lyotropic liquid crystal-based in situ forming gels are proposed as potential long-acting delivery systems for the subcutaneous co-administration of curcumin and piperine. For each of these studies, the drug delivery systems examined are thoroughly investigated, and their characterization is comprehensively documented. In addition, in vitro technological and biological analyses, along with ex vivo or in vivo experiments, are conducted to assess the therapeutic efficacy of the formulations. Overall, the research findings presented in this thesis highlight the advantages of employing NLDDS over more conventional strategies for overcoming drug solubility challenges. Furthermore, the results underscore the importance of technological screening and comprehensive characterization in the design of novel nanosystems with high specificity, tailored to the properties of the drug, the selected route of administration, and the specificities of the therapeutic target
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Spongosome-based co-delivery of curcumin and Piperine: A novel strategy for mitigating pollution-induced skin damage
Full text linkThe present study aims to explore the potential role of curcumin and piperine loaded spongosomes to protect the skin against pollution-induced damage. The hydration of a glyceryl monooleate and sodium cholate thin film, followed by homogenization, led to dispersions with an internal spongiform structure, as demonstrated by cryogenic transmission electron microscopy and small angle X-ray scattering. Spongosome mean diameter measured by photon correlation spectroscopy was roughly 200 nm. Curcumin and piperine were efficiently encapsulated in spongosomes, as demonstrated by ultrafiltration and HPLC analysis. In vitro permeation tests revealed that piperine enhances the penetration of curcumin, suggesting a further improved bioavailability and sustained release. Ex vivo studies using human skin biopsies showed that curcumin and piperine-loaded spongosomes protect the skin against diesel exhaust emissions, preserving the levels of key skin barrier proteins, as filaggrin and involucrin. The formulations exhibited non-irritating properties in human patch tests, supporting their suitability for topical application
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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