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.

• Klíčová slova
• Bioavailability, Encapsulation, Glucan particles, Lymphatic transport, Macrophages, Nilotinib hydrochloride,
• 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
• Názvy látek
• glukany * MeSH
• pyrimidiny MeSH

Currently available methods for cell separation are generally based on fluorescent labeling using either endogenously expressed fluorescent markers or the binding of antibodies or antibody mimetics to surface antigenic epitopes. However, such modification of the target cells represents potential contamination by non-native proteins, which may affect further cell response and be outright undesirable in applications, such as cell expansion for diagnostic or therapeutic applications, including immunotherapy. We present a label- and antibody-free method for separating macrophages from living Drosophila based on their ability to preferentially phagocytose whole yeast glucan particles (GPs). Using a novel deswelling entrapment approach based on spray drying, we have successfully fabricated yeast glucan particles with the previously unachievable content of magnetic iron oxide nanoparticles while retaining their surface features responsible for phagocytosis. We demonstrate that magnetic yeast glucan particles enable macrophage separation at comparable yields to fluorescence-activated cell sorting without compromising their viability or affecting their normal function and gene expression. The use of magnetic yeast glucan particles is broadly applicable to situations where viable macrophages separated from living organisms are subsequently used for analyses, such as gene expression, metabolomics, proteomics, single-cell transcriptomics, or enzymatic activity analysis.

• Klíčová slova
• cell separation, iron oxide nanoparticles, phagocytosis, spray drying, β-glucan particles,
• MeSH
• Drosophila melanogaster metabolismus   MeSH
• glukany * chemie   metabolismus   MeSH
• magnetické jevy MeSH
• makrofágy metabolismus   MeSH
• Saccharomyces cerevisiae * chemie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• glukany * MeSH

Geranylated flavanone diplacone is a flavanone iso- lated from Paulownia tomentosa (Thunb.) Steud. (Paulowniaceae) with anti-inflammatory and antioxidant properties, nevertheless showing high lipophilicity and low solubility in water. Diplacone was therefore used as a model molecule for incorporation into glucan particles (GPs). GPs are prepared by intensive washing of yeast (Saccharomyces cerevisiae) leading to hollow shells consisting of β-(13)/β-(16) glucan mainly. The aim of this study was to compare anti-inflammatory potential of GPs-diplacone composites with the compound itself, GPs themselves and the physical mixture of GPs and diplacone. The cell line THP1-XBlueTM-MD2-CD14 derived from human leukemic monocytes was stimulated with lipopolysaccharide (LPS) from Escherichia coli to trigger inflammatory reaction. The composites of GPs with diplacone significantly decreased the activity of pro-inflammatory transcription factors nuclear factor κB (NF-κB) and activator protein 1 (AP-1).

• Klíčová slova
• AP-1, NF-κB, diplacone, encapsulation, glucan particles, inflammation,
• MeSH
• antiflogistika farmakologie   MeSH
• flavanony farmakologie   MeSH
• glukany chemie   MeSH
• lidé MeSH
• NF-kappa B metabolismus   MeSH
• Saccharomyces cerevisiae chemie   MeSH
• THP-1 buňky MeSH
• transkripční faktor AP-1 metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antiflogistika MeSH
• diplacone MeSH Prohlížeč
• flavanony MeSH
• glukany MeSH
• NF-kappa B MeSH
• transkripční faktor AP-1 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.

• Klíčová slova
• Amorphous solid dispersions, Drug delivery, Poorly soluble drugs, Spray drying, Yeast glucan particles,
• 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
• Názvy látek
• aerosoly MeSH
• beta-glukany MeSH
• ibuprofen MeSH
• kurkumin MeSH
• nosiče léků * 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.

• Klíčová slova
• Amorphous solid dispersion, Incipient wetness impregnation, Slurry evaporation, Spray drying, Two-phase dissolution test, β-glucan,
• 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
• Názvy látek
• beta-glukany MeSH
• kurkumin MeSH
• nosiče léků MeSH
• voda 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.

• Klíčová slova
• Colitis targeting, Curcumin, Inflammation, Yeast glucan particles, β-Glucan,
• 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
• Názvy látek
• antiflogistika MeSH
• cytokiny MeSH
• glukany MeSH
• interleukiny MeSH
• kurkumin MeSH
• nosiče léků MeSH
• síran dextranu MeSH

Glucan particles derived from yeast have been recently proposed as potential drug delivery carriers. Here, we demonstrate the potential of glucan particles for protein delivery in vivo, using the insect Drosophila melanogaster as a model organism. By employing genetic tools, we demonstrate the capacity of yeast glucan particles to spread efficiently through the Drosophila body, to enter macrophages and to deliver an active transcription factor protein successfully. Moreover, the glucan particles were nontoxic and induced only minimal immune response. The injection of glucan particles did not impair the ability of Drosophila to fight and survive infection by pathogenic bacteria. From this study, Drosophila emerges as an excellent model to test and develop drug delivery systems based on glucan particles, specifically aimed to regulate macrophages.

• MeSH
• Drosophila melanogaster imunologie   metabolismus   MeSH
• glukany chemie   metabolismus   MeSH
• kvasinky chemie   MeSH
• lékové transportní systémy * MeSH
• makrofágy cytologie   imunologie   metabolismus   MeSH
• nosiče léků chemie   metabolismus   MeSH
• proteiny Drosophily chemie   metabolismus   MeSH
• transkripční faktory chemie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• GAL4 protein, Drosophila MeSH Prohlížeč
• glukany MeSH
• nosiče léků MeSH
• proteiny Drosophily MeSH
• transkripční faktory 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.

• Klíčová slova
• Curcumin, Drug carrier, Inflammation, Monocytes, Pharmaceutical composite, β-Glucan microparticles,
• 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
• Názvy látek
• antiflogistika MeSH
• glukany MeSH
• IL1B protein, human MeSH Prohlížeč
• interleukin-1beta MeSH
• kurkumin MeSH
• lipopolysacharidy MeSH
• NF-kappa B MeSH
• reaktivní formy kyslíku MeSH
• TNF protein, human MeSH Prohlížeč
• TNF-alfa MeSH
• transkripční faktor AP-1 MeSH

Yeast glucan particles (GPs) are promising agents for the delivery of biologically active compounds as drugs. GPs possess their own biological activities and can act synergistically with their cargo. This study aimed to determine how incorporating artemisinin, ellagic acid, (-)-epigallocatechin gallate, morusin, or trans-resveratrol into GPs affects their anti-inflammatory and antioxidant potential in vitro. Two different methods - slurry evaporation and spray drying - were used to prepare composites (GPs + bioactive compound) and the anti-inflammatory and antioxidative properties of the resultant products were compared. Several of the natural compounds showed the beneficial effects of being combined with GPs. The materials prepared by spray drying showed greater activity than those made using a rotary evaporator. Natural compounds incorporated into yeast GPs showed greater anti-inflammatory potential in vitro than simple suspensions of these compounds as demonstrated by their inhibition of the activity of transcription factors NF-κB/AP-1 and the secretion of the pro-inflammatory cytokine TNF-α.

• Klíčová slova
• Drug carrier, Inflammation, Monocytes, Natural compounds, Pharmaceutical composite, β-glucan microparticles,
• MeSH
• antiflogistika farmakologie   MeSH
• antioxidancia farmakologie   MeSH
• artemisininy farmakologie   MeSH
• cytokiny MeSH
• flavonoidy chemie   farmakologie   MeSH
• glukany chemie   farmakologie   MeSH
• katechin analogy a deriváty   chemie   farmakologie   MeSH
• kyselina ellagová chemie   farmakologie   MeSH
• monocyty účinky léků   MeSH
• NF-kappa B MeSH
• resveratrol chemie   farmakologie   MeSH
• Saccharomyces cerevisiae - proteiny MeSH
• Saccharomyces cerevisiae MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antiflogistika MeSH
• antioxidancia MeSH
• artemisinin MeSH Prohlížeč
• artemisininy MeSH
• cytokiny MeSH
• epigallocatechin gallate MeSH Prohlížeč
• flavonoidy MeSH
• glukany MeSH
• katechin MeSH
• kyselina ellagová MeSH
• morusin MeSH Prohlížeč
• NF-kappa B MeSH
• resveratrol MeSH
• Saccharomyces cerevisiae - proteiny MeSH

Natural compounds offer a wide spectrum of potential active substances, but often they have a poor bioavailability. To increase the bioavailability and bioactivity of the natural anti-inflammatory molecules curcumin and diplacone, we used glucan particles (GPs), hollow shells from Saccharomyces cerevisiae composed mainly of β-1,3-d-glucan. Their indigestibility and relative stability in the gut combined with their immunomodulatory effects makes them promising carriers for such compounds. This study aimed to determine how curcumin and diplacone, either alone or incorporated in GPs, affect the immunomodulatory activity of the latter by assessing the respiratory burst response and the secretion of pro-inflammatory cytokines by primary porcine innate immune cells. Incorporating curcumin and diplacone into GPs by controlled evaporation of the organic solvent substantially reduced the respiratory burst response mediated by GPs. Incorporated curcumin in GPs also reduced GPs mediated secretion of IL-1β and TNF-α by innate immune cells. The obtained results indicate a potentially beneficial effect of the incorporation of curcumin or diplacone into GPs against inflammation.

• Klíčová slova
• Blood immune cells, Curcumin, Diplacone, Glucan particles, Immunomodulatory effect, Inflammation,
• MeSH
• antiflogistika chemie   farmakologie   MeSH
• beta-glukany chemie   izolace a purifikace   farmakologie   MeSH
• flavanony chemie   farmakologie   MeSH
• imunologické faktory chemie   izolace a purifikace   farmakologie   MeSH
• interleukin-1beta metabolismus   MeSH
• kultivované buňky MeSH
• kurkumin chemie   farmakologie   MeSH
• leukocyty mononukleární účinky léků   imunologie   metabolismus   MeSH
• neutrofily účinky léků   imunologie   metabolismus   MeSH
• nosiče léků * MeSH
• příprava léků MeSH
• proteoglykany MeSH
• respirační vzplanutí účinky léků   MeSH
• rozpouštědla chemie   MeSH
• Saccharomyces cerevisiae chemie   MeSH
• Sus scrofa MeSH
• TNF-alfa metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antiflogistika MeSH
• beta-glukany MeSH
• diplacone MeSH Prohlížeč
• flavanony MeSH
• imunologické faktory MeSH
• interleukin-1beta MeSH
• kurkumin MeSH
• nosiče léků * MeSH
• polysaccharide-K MeSH Prohlížeč
• proteoglykany MeSH
• rozpouštědla MeSH
• TNF-alfa MeSH