Kurkumin a jemu příbuzné sloučeniny obsažené v oddenku rostliny kurkumovník dlouhý (Curcuma longa L.) přinášejí mnohočetné benefity pro organismus. Tyto benefity pramení zejména z antioxidačních a protizánětlivých vlastností kurkuminu. Z těchto účinků mohou profitovat lidé v rámci prevence a zvládání mnoha nepříznivých zdravotních stavů. Naději přinášejí i dosavadní studie o významu kurkuminu v managementu onemocnění covid-19. Pro těhotné je ale podávání kurkuminu stále kontraindikováno. Nové přípravky zlepšující biodostupnost této látky potenciál kurkuminu ještě umocňují.
Curcumin and its related compounds in the rhizome of the turmeric plant (Curcuma longa L.) bring multiple benefits for the organism. Anti-inflammatory and antioxidant properties of curcumin are considered to be the most important. There are reports confirming the preventive and ameliorating effects of this substance against different adverse health complications. Studies with focus on the management of the covid-19 disease also raise hope. However, curcumin is still contraindicated in pregnant women. New formulations that improve the bioavailability of this substance further enhance the potential of curcumin.
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
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
Purpose: Due to the shortcomings of nanocarriers, the development of carrier-free nanodelivery systems has attracted more and more attention in cancer treatment. However, there are few studies on carrier-free nanosystems that can simultaneously achieve monitoring functions. Here a multifunctional carrier-free nanosystem loaded with curcumin and irinotecan hydrochloride was established for the treatment and monitoring of gastric cancer. Methods: In this study, an irinotecan hydrochloride-curcumin nanosystem in the early stage (the system is named SICN) was prepared. Based on the fluorescence of curcumin, flow cytometry, laser confocal microscopy, and zebrafish fluorescence imaging were used to study the monitoring function of SICN in vivo and in vitro. In addition, HGC-27 human gastric cancer cells were used to study SICN cytotoxicity. Results: Flow cytometry and zebrafish fluorescence imaging monitoring results showed that the uptake of SICN was significantly higher than free curcumin, and the excretion rate was lower. SICN had higher accumulation and retention in cells and zebrafish. Laser confocal microscopy monitoring results showed that SICN was internalized into HGC-27 cells through multiple pathways, including macropinocytosis, caveolin, and clathrin-mediated and clathrin -independent endocytosis, and distributed intracellularly throughout the whole cytoplasm, including lysosomes and Golgi apparatus. In vitro cell experiments showed that SICN nanoparticles were more toxic than single components, and HGC-27 cells had more absorption and higher toxicity to nanoparticles under slightly acidic conditions. Conclusion: SICN is a promising carrier-free nanoparticle, and the combination of two single-component therapies can exert a synergistic antitumor effect. When exposed to a tumor acidic environment, SICN showed stronger cytotoxicity due to charge conversion. More importantly, the nanoparticles' self-monitoring function has been developed, opening up new ideas for combined tumor therapy.
- MeSH
- apoptóza účinky léků MeSH
- buněčná smrt účinky léků MeSH
- buněčný cyklus účinky léků MeSH
- dánio pruhované MeSH
- endocytóza účinky léků MeSH
- fluorescence MeSH
- irinotekan farmakologie terapeutické užití MeSH
- kurkumin aplikace a dávkování farmakologie terapeutické užití MeSH
- lékové transportní systémy * MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nádory farmakoterapie MeSH
- nanočástice chemie MeSH
- nosiče léků MeSH
- uvolňování léčiv MeSH
- velikost částic MeSH
- zobrazování trojrozměrné MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
In our previous research, we concluded that polymeric micelles based on hyaluronic acid are able to penetrate into the deeper layers of skin tissue. The aim of this work was to characterize the mechanisms involved in the uptake by skin cells, which is important for understanding the influence of the carrier composition on the drug penetration. To reach this goal, we used micelles encapsulating curcumin made of oleyl-hyaluronan (HAC18:1) and hexyl-hyaluronan (HAC6) covalently linked with fluorescent Nile Blue. This labeling enabled us to track the micelle-forming derivative and also micelle payload into the keratinocytes and fibroblasts by fluorescent microscopy and flow cytometry. The regulation of both the passive and active cellular uptake was used to determine the mechanism of micelle internalization. Furthermore, the changes of membrane fluidity were measured for these derivatives by FRAP. Using these methods we concluded that carriers entered the cells using both active and passive transport. Passive transport was facilitated by the affinity of the carrier to the cell membrane, especially in the case of HAC18:1 carrier, which changed significantly the membrane fluidity. The active transport was dependent on cell type, but mainly driven by the clathrin-mediated endocytosis and macropinocytosis. Surprisingly, the main HA receptor, CD44, was not involved in the uptake. We can conclude that these carrier systems could be used for the local transport of active substances or hydrophobic drugs into the skin cells using the advantage of passive transport of oleyl-HA derivative.
- MeSH
- aplikace lokální MeSH
- endocytóza MeSH
- fibroblasty metabolismus MeSH
- keratinocyty metabolismus MeSH
- kožní absorpce * MeSH
- kultivované buňky MeSH
- kurkumin aplikace a dávkování MeSH
- kůže metabolismus MeSH
- kyselina hyaluronová aplikace a dávkování MeSH
- lékové transportní systémy * MeSH
- lidé MeSH
- lyzozomy metabolismus MeSH
- polymery aplikace a dávkování MeSH
- Check Tag
- lidé 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
A highly water soluble, nano-formulated curcumin was used for the treatment of the experimental model of spinal cord injury (SCI) in rats. Nanocurcumin and a vehicle nanocarrier as a control, were delivered both locally, immediately after the spinal cord injury, and intraperitoneally during the 4 consecutive weeks after SCI. The efficacy of the treatment was assessed using behavioral tests, which were performed during the experiment, weekly for 9 weeks. The behavioral tests (BBB, flat beam test, rotarod, motoRater) revealed a significant improvement in the nanocurcumin treated group, compared to the nanocarrier control. An immunohistochemical analysis of the spinal cord tissue was performed at the end of the experiment and this proved a significant preservation of the white matter tissue, a reduced area of glial scaring and a higher amount of newly sprouted axons in the nanocurcumin treated group. The expression of endogenous genes (Sort1, Fgf2, Irf5, Mrc1, Olig2, Casp3, Gap43, Gfap, Vegf, Nfkβ) and interleukins (IL-1β, TNF-α, IL-6, IL-12, CCL-5, IL-11, IL-10, IL-13) was evaluated by qPCR and showed changes in the expression of the inflammatory cytokines in the first two weeks after SCI.
- MeSH
- bílá hmota účinky léků metabolismus patologie MeSH
- jizva farmakoterapie metabolismus patologie MeSH
- krysa rodu rattus MeSH
- kurkumin aplikace a dávkování MeSH
- mediátory zánětu antagonisté a inhibitory metabolismus MeSH
- nanočástice aplikace a dávkování MeSH
- neuroglie účinky léků metabolismus patologie MeSH
- poranění míchy farmakoterapie metabolismus patologie MeSH
- potkani Wistar MeSH
- příprava léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Advanced drug delivery systems (DDS) are easily designed following a photoiterative strategy. Multifunctional polymers are obtained by coupling building blocks of interest to an alkynated poly(ε-caprolactone) (PCL) platform via an efficient thiol-yne photoaddition. Fine-tuning over the design is achieved, as illustrated with targeting and enzyme-responsive DDS.
- MeSH
- alkyny chemie MeSH
- fotochemické procesy * MeSH
- HEK293 buňky MeSH
- kurkumin aplikace a dávkování chemie MeSH
- lékové transportní systémy metody MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nanostruktury aplikace a dávkování chemie MeSH
- polyestery chemie MeSH
- polyethylenglykoly chemie MeSH
- protinádorové látky aplikace a dávkování chemie MeSH
- sulfhydrylové sloučeniny chemie MeSH
- viabilita buněk účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Východiska: Kurkumovník dlouhý (Curcuma longa) je rostlina, která je známá především jako součást kari koření. Hlavní obsahovou látkou zodpovídající za většinu biologických účinků je polyfenol kurkumin. Cíl: Tato přehledová práce má za cíl poskytnout ucelený obraz o výsledcích studií, které se věnují léčebnému využití kurkuminu v onkologii. Preklinické studie poskytují informace o mechanizmech účinku a případné toxicitě kurkuminu. Klinické studie jsou zatím zaměřeny především na bezpečnost, farmakokinetiku a stanovení optimální dávky kurkuminu, narůstá ovšem i počet studií, které hodnotí protinádorové a onkopreventivní účinky kurkuminu, případně podpůrný účinek při řešení nežádoucích účinků chemoterapeutik a radioterapie. Jejich výsledky jsou optimistické a povzbuzují k dalšímu výzkumu. Největším problémem léčby kurkuminem je jeho nízká biologická dostupnost, ze které vyplývá nutnost použití vysokých dávek. Z tohoto důvodu se jeví jako nejvýhodnější využít lokálního působení kurkuminu ve střevě, na sliznicích nebo na kůži, tedy tam, kde odpadá nutnost systémového působení. Současné poznatky vyzdvihují zejména bezpečnost kurkuminu, a to až do dávek několika gramů. Dle dostupných informací lze užívání kurkuminu jako doplňku stravy doporučit lidem, kteří mají zvýšené riziko onkologického onemocnění, jako jsou např. silní kuřáci, nebo pacientům s prekancerózními lézemi. Vzhledem k již zmíněné bezpečnosti je možno kurkumin doporučit i onkologickým pacientům, kteří vyžadují přírodní léčbu.
Background: Turmeric (Curcuma longa) is mainly known as a constituent of curry spice. The main active ingredient, responsible for most of its biological effects, is the polyphenol curcumin. Aim: This review aims to provide a comprehensive overview of studies evaluating the benefits of therapeutic curcumin use in oncology. Preclinical studies provide information on the mechanism of action and potential toxicity of curcumin. Clinical studies have so far focused mainly on safety, pharmacokinetics, and determination of the optimal dose of curcumin. However, there are a growing number of trials evaluating the anti-tumor and oncopreventive effects of curcumin and its effect in alleviating the adverse effects of chemotherapeutics and radiotherapy. So far, the results have been optimistic and should encourage further research. The main problem associated with curcumin treatment is its low oral bioavailability, which means it must administrated at high doses to be effective. Therefore, curcumin is more appropriate as a local treatment for areas such as the intestine, mucous membrane, or the skin, where there is no need for a strong systemic effect. Curcumin has a good safety profile when used up to several grams. Curcumin can also be used as a food supplement for people at increased risk of oncological disease, such as heavy smokers or those with pre-cancerous lesions. Due to its good safety profile, curcumin can be recommended to oncological patients who request a natural treatment.
- MeSH
- apoptóza MeSH
- chemoprofylaxe MeSH
- fytoterapie MeSH
- klinické zkoušky jako téma MeSH
- komplementární terapie MeSH
- kurkumin * aplikace a dávkování farmakokinetika farmakologie terapeutické užití MeSH
- lidé MeSH
- modely u zvířat MeSH
- nádory * prevence a kontrola terapie MeSH
- protinádorové látky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
Nanocrystals have received considerable attention in dermal application due to their ability to enhance delivery to the skin and overcome bioavailability issues caused by poor water and oil drug solubility. The objective of this study was to investigate the effect of nanocrystals on the mechanism of penetration behavior of curcumin as a model drug. Curcumin nanocrystals were produced by the smartCrystals® process, i.e. bead milling followed by high pressure homogenization. The mean particle size of the curcumin crystals was about 200nm. Stabilization was performed with alkyl polyglycoside surfactants. The distribution of curcumin within the skin was determined in vitro on cross-sections of porcine skin and visualized by fluorescent microscopy. The skin penetration profile was analyzed for the curcumin nanosuspension with decreasing concentrations (2%, 0.2%, 0.02% and 0.002% by weight) and compared to nanocrystals in a viscous hydroxypropylcellulose (HPC) gel. This study demonstrated there was minor difference between low viscous nanosuspension and the gel, but low viscosity seemed to favor skin penetration. Localization of curcumin was observed in the hair follicles, also contributing to skin uptake. Looking at the penetration of curcumin from formulations with decreasing nanocrystal concentration, formulations with 2%, 0.2% and 0.02% showed a similar penetration profile, whereas a significantly weaker fluorescence was observed in the case of a formulation containing 0.002% of curcumin nanocrystals. In this study we have shown that curcumin nanocrystals prepared by the smartCrystal® process are promising carriers in dermal application and furthermore, we identified the ideal concentration of 0.02% nanocrystals in dermal formulations. The comprehensive study of decreasing curcumin concentration in formulations revealed that the saturation solubility (Cs) is not the only determining factor for the penetration. A new mechanism based also on the concentration of the nanocrystals on skin surface was proposed.
