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Neue Formulierungsstrategien für eine verbesserte dermale Verabreichung von Curcumin
No full textDermal drug delivery is a preferred administration route for bypassing first-
pass metabolism, minimizing systemic side effects and delivering local or system ic
benefits. Formulation strategies are often employed to improve drug solubility and
penetration, enhancing dermal bioavailability. Many dermal drugs face solubility
challenges, necessitating advanced formulation strategies. Curcumin is a natural
bioactive compound derived from the turmeric plant Curcum a longa L., and has been
widely used due to its therapeutic benefits against dermal conditions. However, it is
characterized by low solubility and bioavailability. Therefore, dermal curcumin
formulation strategies are often employed to improve its limitations. The established
ex vivo porcine ear model has been frequently used to test various formulations,
providing insights into effective strategies that preserve skin physiology, improve
penetration and elucidate penetration mechanism. Expanding on previous findings, a
systemic study of different classic and novel formulation strategies is necessary to
evaluate their effectiveness in enhancing dermal delivery of poorly water-soluble
drugs. In this context, plant-based extracellular vesicles, plantCrystals, and
microemulsion formulations were selected to be investigated to improve the solubility
and bio-efficacy of a poorly water-soluble drug, curcumin.
The first project studied the impact of classical plant-derived extracellular
vesicles (EVs) and plantCrystals-extracellular vesicles (PCEVs) on curcumin dermal
delivery using an ex vivo porcine ear skin model. Two study designs were employed,
aiming to determine the dermatokinetics of curcumin penetration, and to investigate
penetration efficacy and depth. EVs were isolated through classical methods, while
PCEVs were prepared via bead milling, with curcumin incorporated either during or
after PCEVs formation, resulting in curcumin-loaded and curcumin-added PCEVs,
respectively. Dermatokinetics indicated that curcumin particles facilitated penetration
through a particle-assisted mechanism. Upon evaporation of the dispersion medium,
an aqueous meniscus formed between the particles and skin, creating a high local
concentration gradient that enhanced drug delivery. This effect was most pronounced
in curcumin-loaded PCEVs, where smaller and more abundant particles maximized
the contact area. Curcumin-loaded PCEVs achieved a significantly higher penetration efficacy compared to curcumin-added PCEVs and curcumin-loaded EVs. Its also
exhibited greatest penetration depth, whereas curcumin delivered from EVs remained
in the stratum corneum. The data revealed that incorporating curcumin during PCEVs
production is critical for maximizing penetration efficacy. The findings of this project
confirm the promise of PCEVs as an effective delivery system for curcumin and similar
poorly soluble compounds, highlighting bead milling as a superior strategy over
classical EVs methods. This formulation presented a plant-based and nontoxic
approach as a carrier for dermal drug delivery, thereby it offers a great potential for
pharmaceutical development and further exploration of different potential plants to
improve the solubility and bioavailability of poorly water-soluble drugs.
The second project studied microemulsions as a nano-scaled systems for
improving curcumin dermal delivery using the ex vivo porcine ear model. The study
investigated how microemulsion components and their varying concentration s
influence the penetration efficacy. Nine of curcumin microemulsion formulations
were prepared with varying ratios of the oily and water phases and the surfactants
mixture (surfactant and co-surfactant (Smix)). Formulations with higher oily phase
content exhibited larger hydrodynamic sizes and broader size distribution, while
those with higher Smix and water content demonstrated smaller sizes and narrower
size distribution. Results showed enhanced penetration efficacy of curcumin was
associated with higher ethanol and water ratios. This highlights the role of
composition in modulating curcumin transport through the skin. Bench controls,
including curcumin solutions and dispersion were prepared to elucidate the vehicle
effect on curcumin delivery. Based on the data obtained, it can be assumed that the
curcumin penetration from microemulsion formulations revealed overlappin g
penetration mechanisms influenced by the formulation’s composition. While
microemulsion formulations effectively delivered curcumin to the upper epiderm is,
their limited penetration depth restricts their use for targeting the dermis. These
findings provide a foundation for optimizing microemulsion systems to enhance the
dermal delivery of poorly soluble active compounds like curcumin.Die dermale Arzneimittelverabreichung ist eine bevorzugte
Applikationsroute. Sie umgeht den First-Pass-Metabolismus, minimiert systemische
Nebenwirkungen, und erzielt lokale als auch systemische Vorteile
Formulierungsstrategien werden häufig eingesetzt, um die Löslichkeit und
Penetration von Wirkstoffen zu verbessern und damit die dermale Bioverfügbark eit
zu erhöhen. Viele dermale Wirkstoffe weisen Löslichkeitsprobleme auf, weshalb
fortschrittliche Formulierungen erforderlich sind.
Curcumin, ein bioaktiver Naturstoff, extrahiert aus Curcum a longa L., ist für seine
therapeutischen Vorteile bekannt, zeigt jedoch eine geringe Wasserlöslichkeit und
Bioverfügbarkeit. Daher werden spezifische Formulierungsstrategien entwickelt, um
diese Einschränkungen zu überwinden. Das ex vivo-Schweineohrhautmodell dient
häufig zur Untersuchung von Formulierungen, da es die Hautphysiologie erhält und
die Penetration sowie deren Mechanismen darstellen. Eine systematische Analyse
klassischer und innovativer Formulierungsansätze ist notwendig, um deren
Wirksamkeit für die dermale Verabreichung schlecht wasserlöslicher Wirkstoffe zu
bewerten. In diesem Kontext wurden pflanzenbasierte extrazelluläre Vesikel,
PlantCrystals und Mikroemulsionen untersucht, um die Löslichkeit und
Bioverfügbarkeit von Curcumin zu verbessern.
Im ersten Projekt wurde der Einfluss klassischer pflanzlicher extrazellulärer
Vesikel (EVs) und PlantCrystals-extrazellulärer Vesikel (PCEVs) auf die dermale
Aufnahme von Curcumin analysiert. Es wurden zwei Studiendesigns angewandt, um
die Dermatokinetik der Curcumin-Penetration zu bestimmen und die
Penetrationswirksamkeit und -tiefe zu untersuchen. EVs wurden klassisch isoliert,
während PCEVs mit dem Verfahren des Bead Millings hergestellt wurden. Curcumin
wurde entweder während oder nach der PCEV-Bildung eingebracht, was zu
curcuminbeladenen bzw. curcuminzugesetzten PCEVs führte. Die Analysen zeigten,
dass Curcuminpartikel die Penetration durch einen partikelvermittelt en
Mechanismus erleichtern. Nach der Verdunstung des Dispersionsmediums entstand
ein hoher lokaler Konzentrationsgradient, der die Wirkstoffaufnahme förderte. Dieser
Effekt war besonders bei curcuminbeladenen PCEVs ausgeprägt, die kleinere und
zahlreichere Partikel aufwiesen. Die curcuminbeladenen PCEVs erreichten eine signifikant höhere Penetrationseffizienz als curcuminzugesetzte PCEVs und
curcuminbeladene EVs. Zudem zeigten sie die größte Penetrationstiefe, währen d
Curcumin aus EVs hauptsächlich in dem Stratum corneum verblieb. Die Ergebnisse
belegen, dass die Integration von Curcumin während der PCEV-Produktion
entscheidend für eine maximale Penetrationseffizienz ist. Diese Studie bestätigt das
Potenzial von PCEVs als effizientes Trägersystem für schwer lösliche Wirkstoffe und
hebt das Verfahren des Bead Millings als überlegene Strategie gegenüber klassischen
EV-Methoden hervor. Diese pflanzenbasierte, ungiftige Formulierung bietet großes
Potenzial für die pharmazeutische Entwicklung und die Erforschung weiterer
Pflanzenextrakte zur Verbesserung der Löslichkeit und Bioverfügbarkeit.
Im zweiten Projekt wurden Mikroemulsionen als nanoskalige Systeme zur
Verbesserung der dermalen Curcumin-Freisetzung untersucht. Ziel war es, den
Einfluss der Mikroemulsionskom ponenten und ihrer Konzentrationsverhältnisse auf
die Penetrationseffizienz zu analysieren. Es wurden neun verschiedene Curcumin-
Mikroemulsionsformulierungen hergestellt, wobei das Verhältnis von Öl-,
Wasserphase und Tensidgemisch (Tensid und Co-Tensid (Smix)) variiert wurde.
Formulierungen mit höherem Ölanteil zeigten größere Partikelgrößen und eine
breitere Größenverteilung, während Formulierungen mit höheren Smix- und
Wasseranteilen kleinere Partikel und eine engere Größenverteilung aufwiesen. Die
Ergebnisse zeigten, dass eine erhöhte Penetrationseffizienz mit höheren Ethanol- und
Wasseranteilen korrelierte, was die Bedeutung der Formulierungszusammensetzun g
für den Transport von Curcumin durch die Haut unterstreicht. Zur besseren
Einordnung der Ergebnisse wurden Curcuminlösungen und -dispersionen als
Kontrollen untersucht. Die Daten legen nahe, dass die Penetration von Curcumin aus
Mikroemulsionsformulierungen überlappende Penetrationsmechanismen aufweist,
die von der Zusammensetzung der Formulierung beeinflusst werden. Während
Mikroemulsionen Curcumin effektiv in die obere Epidermis transportierten, blieb die
Penetrationstiefe begrenzt, was ihren Einsatz zur gezielten Wirkstofffreisetzung in die
Dermis einschränkt. Diese Erkenntnisse bilden eine Grundlage für die Optimierung
von Mikroemulsionssystemen zur Verbesserung der dermalen Verabreichung schwer
löslicher Wirkstoffe wie Curcumin
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe 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
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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