Particle size reduction to sub-micrometer dimensions in stirred media mills is an increasingly common formulation strategy used for improving the bioavailability of poorly aqueous soluble active pharmaceutical ingredients (APIs). Due to their hydrophobic character, the API particles need to be stabilised by a surfactant in order to form a stable nano-suspension. This work is concerned with the understanding of an undesired phenomenon often encountered during the development and scale-up of wet nano-milling processes for hydrophobic APIs - the formation of foams. We investigate the microstructure, rheology and stability of these foams, and find them to be Pickering foams stabilised by solid particles at the gas-liquid interface rather than by a surfactant. By exploring the effect of surfactant concentration on the on-set of foaming in conjunction with the milling kinetics, we find a relationship between the specific surface area of the nano-suspension, the quantity of surfactant present in the formulation and the occurrence of foaming. We propose a mechanistic explanation of foam formation, and find that in order to prevent foaming, a large surfactant excess of approx. 100x above the critical micelle concentration has to be present in the solution in order to ensure a sufficiently rapid coverage of freshly exposed hydrophobic surfaces formed during the wet nano-milling process.

• MeSH
• biologická dostupnost MeSH
• farmaceutická technologie metody   MeSH
• hydrofobní a hydrofilní interakce MeSH
• nanočástice chemie   MeSH
• povrchově aktivní látky chemie   MeSH
• roztoky chemie   MeSH
• suspenze chemie   MeSH
• velikost částic MeSH
• Publikační typ
• časopisecké články MeSH

Glucan particles (GPs) from Saccharomyces cerevisiae are hollow shells that are composed mainly of β-1,3-d-glucan, which has demonstrated immunomodulatory and anti-inflammatory potential both in vitro and in vivo. Curcumin is a natural hydrophobic phenolic compound, which possesses a significant anti-inflammatory effect and is used as supportive therapy in the treatment of many inflammatory diseases. The aim of this study is to evaluate the possible synergic effect and other benefits of the co-application of GPs and curcumin in the form of pharmaceutical composites. GP/curcumin composites were prepared using controlled evaporation of the organic solvent and their anti-oxidative effect and anti-inflammatory potential were tested on THP1‑XBlue™‑MD2‑CD14 human monocytes cell line. The anti-oxidative effect was measured on pyocyanin-stimulated cells in vitro and the NF-κB/AP-1 signaling pathway on lipopolysaccharide pre-treated monocytes was chosen for anti-inflammatory assays. The secretion of pro-inflammatory cytokines TNF-α and IL-1β was evaluated as well. Results mostly showed a pro-oxidative activity of empty GPs, however, pharmaceutical composites demonstrated an anti-oxidative effect. The activity of NF-κB/AP-1 was substantially decreased by the tested GP/curcumin composites, which also caused the attenuation of cytokines secretion. The obtained results indicate a beneficial effect of the incorporation of curcumin into GPs.

• MeSH
• antiflogistika aplikace a dávkování   chemie   MeSH
• glukany aplikace a dávkování   chemie   MeSH
• interleukin-1beta metabolismus   MeSH
• kurkumin aplikace a dávkování   chemie   MeSH
• lidé MeSH
• lipopolysacharidy MeSH
• makrofágy účinky léků   metabolismus   MeSH
• monocyty účinky léků   metabolismus   MeSH
• NF-kappa B metabolismus   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• Saccharomyces cerevisiae MeSH
• THP-1 buňky MeSH
• TNF-alfa metabolismus   MeSH
• transkripční faktor AP-1 metabolismus   MeSH
• viabilita buněk účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

In this work, novel amorphous solid dispersions based on yeast glucan particles were produced. Yeast glucan particles are hollow and porous, and they are mainly composed of amorphous polysaccharides. We hypothesized that these particles are suitable candidates for the amorphization of drugs with low water solubility. Model drugs ibuprofen and curcumin were successfully encapsulated in glucan particles by spray drying. Different spray-drying parameters were tested to evaluate the influence of atomizing droplet size and initial solid content on encapsulation efficiency. It was shown that higher solid content and, more significantly, larger droplet sizes lead to higher encapsulation efficiencies. The encapsulation efficiency of ibuprofen (10 wt%) into glucan particles was considerably improved from 41.3 ± 0.5% to 64.3 ± 0.2% by increasing initial solid content and droplet size with the two-fluid nozzle. The spray drying process was further optimized by using the ultrasonic nozzle and it was possible to achieve complete encapsulation of ibuprofen and curcumin without any precipitation of the active compound outside of the glucan particles. Overall, it was possible to produce completely amorphous composites with outstanding wettability and dispersion properties, and with significantly faster dissolution rates when compared to the micronized crude drug.

• MeSH
• aerosoly MeSH
• beta-glukany chemie   izolace a purifikace   MeSH
• ibuprofen chemie   MeSH
• kinetika MeSH
• kurkumin chemie   MeSH
• nosiče léků * MeSH
• příprava léků MeSH
• rozpustnost MeSH
• Saccharomyces cerevisiae chemie   MeSH
• ultrazvuk * MeSH
• uvolňování léčiv MeSH
• velikost částic MeSH
• vysoušení * MeSH
• Publikační typ
• časopisecké články MeSH

Yeast glucan particles are porous polysaccharide cell walls extracted from Saccharomyces cerevisiae. Being mildly immunogenic, they are efficiently phagocytosed and have therefore been proposed as possible vehicles for drug delivery. Using curcumin as a model poorly water-soluble drug, a systematic comparison of three different physical loading methods - incipient wetness impregnation, slurry evaporation, and spray drying - was carried out and their influence on the particle morphology, encapsulation efficiency, amorphous drug content and release kinetics was evaluated. It was found that yeast glucan particles can contain up to 30% wt. of curcumin in the amorphous form when prepared by slurry evaporation. The dissolution of curcumin from glucan particles lead to a supersaturated solution in asimilar way as amorphous solid dispersions do, despite the fact that glucan particles themselves do not dissolve. Bi-phasic dissolution tests revealed up to 4-fold acceleration of curcumin dissolution rate from amorphous glucan particles compared to its crystalline form. Crucially, glucan particles were shown to retain the ability to be recognised and phagocytosed even after drug encapsulation.

• MeSH
• beta-glukany chemie   MeSH
• farmaceutická chemie metody   MeSH
• kinetika MeSH
• krystalizace MeSH
• kurkumin aplikace a dávkování   chemie   MeSH
• lékové transportní systémy * MeSH
• nosiče léků chemie   MeSH
• příprava léků metody   MeSH
• rozpustnost MeSH
• uvolňování léčiv MeSH
• voda chemie   MeSH
• Publikační typ
• časopisecké články MeSH

The goal of this work was to assess the usability of yeast glucan particles (GPs) as carriers for curcumin and determine the beneficial effect of a pharmacological composite of curcumin in GPs on dextran sulfate sodium induced colitis in rats. The assessment of the anti-inflammatory effect of particular substances was evaluated on the basis of the calculated disease activity index and by assessment of cytokines and enzymes from the gut tissue - tumor necrosis factor α (TNF-α), transforming growth factor β1, interleukin (IL)-1β, IL-6, IL-10, IL-17, catalase, superoxide dismutase 2, myeloperoxidase (MPO), and matrix metalloproteinase 9. Composites of GPs with incorporated curcumin showed promising results with the capability to lower symptoms of colitis and significantly decrease the production of pro-inflammatory cytokines TNF-α, IL-1β, IL-6, and the activity of MPO, as well. The anti-inflammatory effect of the composites was greater than those of pure GPs or curcumin.

• MeSH
• antiflogistika aplikace a dávkování   terapeutické užití   MeSH
• cytokiny metabolismus   MeSH
• glukany aplikace a dávkování   terapeutické užití   MeSH
• interleukiny metabolismus   MeSH
• kolitida chemicky indukované   farmakoterapie   MeSH
• krysa rodu rattus MeSH
• kurkumin aplikace a dávkování   terapeutické užití   MeSH
• nosiče léků terapeutické užití   MeSH
• potkani Wistar MeSH
• Saccharomyces cerevisiae metabolismus   MeSH
• síran dextranu MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Nilotinib is a selective tyrosine-kinase inhibitor approved for the treatment of chronic myeloid leukemia. It is poorly soluble in aqueous media and has a low oral bioavailability. Nilotinib encapsulation into yeast glucan particles (GPs) was investigated in this work as a means of increasing bioavailability. The amorphization of nilotinib in GPs resulted in an increased dissolution rate, which was confirmed by in vitro experiments using biorelevant dissolution media. Simultaneously, GPs containing nilotinib were effectively taken up by macrophages, which was quantified in vitro on cell cultures. The overall oral bioavailability in a rat model was approximately 39 % for nilotinib delivered in a reference formulation (Tasigna) and was almost doubled when delivered in GPs. The contribution of glucan particles to the lymphatic transport of nilotinib was quantified. When delivered by GPs, cumulative nilotinib absorption via the lymphatic system increased by a factor of 10.8 compared to the reference, but still represented arelative bioavailability of only 1.12 %. The cumulative uptake of GPs in the lymph was found to be 0.54 mg after a single dose of 50 mg. Yeast glucan particles can therefore serve as a drug delivery vehicle with a dual function: dissolution rate enhancement by amorphization, and, to asmaller extent, lymphatic delivery due to macrophage uptake.

• MeSH
• aplikace orální MeSH
• glukany * MeSH
• krysa rodu rattus MeSH
• pyrimidiny MeSH
• Saccharomyces cerevisiae * MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Ačkoli se rodina Havlova těší velké pozornosti a osudy jednotlivých členů byly již literárně zpracovány, životu Ivana M. Havla se dosud nedostalo ze strany historiků systematického zájmu. Právě to bylo impulzem ke vzniku historické biografie, která kombinuje archivní a orálněhistorický výzkum. Vzniká tak obraz člověka, který není pouhým souhrnem biografických dat, ale živoucí osobností, která promlouvá skrze souvislosti a prostředí, v němž se pohybovala. Monografie se snaží čtenáři přiblížit život významného pokračovatele rodu, ale též vědce, intelektuála a autora, který se pohyboval v několika různých, zdánlivě nesourodých prostředích, na pomezí oficiální a neoficiální sféry, člověka, jenž propojuje vědu a umění. Snaha o porozumění osobnosti Ivana M. Havla je přitom doprovázena vědomím širších, především rodinných souvislostí, sahajících až do počátku dvacátého století.; Životní osudy disidenta a vědce Ivana M. Havla.

• MeSH
• environmentální zdraví MeSH
• hygiena MeSH

• Konspekt
• Veřejné zdraví a hygiena
• NLK Obory
• hygiena
• environmentální vědy

Tato kniha je průvodcem pro všechny, kteří žijí zdravě a ještě zdravěji chtějí zemřít. Vypráví o neobvyklých symptomech nemocí a ještě neobvyklejších metodách léčby, o nehorázných chybných diagnózách, šílených vedlejších účincích a zázračných spontánních uzdraveních. A nezáleží na tom, že právě vy nemáte ani promodralou kůži, nůž v zádech, dvě krevní skupiny nebo prostě něco podobně bizarního, po těchto lekcích budete vědět, že uzdravit se dá vždycky. Mnohdy dokonce i bez doktora; Tato kniha je průvodcem pro všechny, kteří žijí zdravě a ještě zdravěji chtějí zemřít. Vypráví o neobvyklých symptomech nemocí a ještě neobvyklejších metodách léčby, o nehorázných chybných diagnózách, šílených vedlejších účincích a zázračných spontánních uzdraveních. A nezáleží na tom, že právě vy nemáte ani promodralou kůži, nůž v zádech, dvě krevní skupiny nebo prostě něco podobně bizarního, po těchto lekcích budete vědět, že uzdravit se dá vždycky. Mnohdy dokonce i bez doktora.

• MeSH
• lékařství v literatuře MeSH
• Publikační typ
• populární práce MeSH

• Konspekt
• Česká próza
• NLK Obory
• humanitní vědy a umění
• lékařství