Polyelectrolyte layer-by-layer (LbL) films that disintegrate under physiological conditions are intensively studied as coatings to enable the release of bioactive components. Herein, we report on the interactions and pH-stability of LbL films composed of chitosan (CH) or N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (CMCH) and tannic acid (TA), employed to guarantee the film disintegration. The self-assembly of TA with CH and CMCH at pH 5 and with CMCH at pH 7.4 were proven by turbidimetric, surface plasmon resonance and UV-Vis analyses. The LbL films exhibited pH-dependent properties; CMCH/TA films prepared at pH 7.4 showed exponential growth as well as a higher layer thickness and surface roughness, whereas films prepared at pH 5 grew linearly and were smoother. The film stability varied with the pH used for film assembly; CH/TA films assembled at pH 5 were unstable at pH 8.5, whereas CMCH/TA films assembled at pH 7.4 disintegrated at pH 4. All films exhibited a similar disassembly at pH 7.4. The coatings reduced the adhesion of E. coli and S. aureus by approximately 80%. CMCH-terminated CMCH/TA films were more resistant to bacterial adhesion, whereas CH-terminated CH/TA films demonstrated stronger killing activity. The prepared pH-triggered decomposable LbL films could be used as degradable coatings that allow the release of therapeutics for biomedical applications and also prevent bacterial adhesion.
- MeSH
- antibakteriální látky farmakologie MeSH
- biokompatibilní materiály chemie farmakologie MeSH
- chitosan chemie MeSH
- Escherichia coli účinky léků MeSH
- film jako téma MeSH
- koncentrace vodíkových iontů MeSH
- Staphylococcus aureus účinky léků MeSH
- taniny chemie MeSH
- Publikační typ
- časopisecké články MeSH
PURPOSE: The aim was to design and thoroughly characterize monodisperse Fe3O4@SiO2-Ag nanoparticles with strong antibacterial properties, which makes them a candidate for targeting bacterial infections. METHODS: The monodisperse Fe3O4 nanoparticles were prepared by oleic acid-stabilized thermal decomposition of Fe(III) oleate; the particles were coated with silica shell using a water-in-oil reverse microemulsion, involving hydrolysis and condensation of tetramethyl orthosilicate. Resulting Fe3O4@SiO2 particles were modified by (3-mercaptopropyl)trimethoxysilane to introduce 1.1 mmol SH/g. Finally, the Fe3O4@SiO2-SH nanoparticles were decorated with silver nanoclusters formed by reduction of silver nitrate with NaBH4. The particles were analyzed by FTIR, X-ray photoelectron and atomic absorption spectroscopy, dynamic light scattering and vibrating sample magnetometry. The antibacterial activity of the Fe3O4@SiO2 and Fe3O4@SiO2-Ag nanoparticles was tested against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli bacteria cultivated on Luria agar plates or in Luria broth. RESULTS: The superparamagnetic Fe3O4@SiO2-Ag nanoparticles (21 nm in diameter; saturation magnetization 26 A∙m2/kg) were successfully obtained and characterized. Inhibitory and toxic effects against bacteria were documented by incubation of the Fe3O4@SiO2-Ag nanoparticles with Staphylococcus aureus and Escherichia coli. CONCLUSIONS: The combination of magnetic properties together with bactericidal effects is suitable for the disinfection of medical instruments, water purification, food packaging, etc.
- MeSH
- antibakteriální látky chemie farmakologie MeSH
- Escherichia coli účinky léků MeSH
- kyselina olejová chemie MeSH
- magnetické nanočástice chemie MeSH
- oxid křemičitý chemie MeSH
- povrchové vlastnosti MeSH
- silany chemie MeSH
- Staphylococcus aureus účinky léků MeSH
- stříbro chemie farmakologie MeSH
- velikost částic MeSH
- Publikační typ
- časopisecké články MeSH
Poly(d,l-lactide)/polyethylene glycol (PLA/PEG) micro/nanofibers loaded with paclitaxel (PTX, 10 wt%) were prepared by needless electrospinning technology, which allows large scale production for real medicinal practice. The fiber structure and properties were investigated by several methods including scanning electron microscopy, nitrogen adsorption/desorption isotherm measurements, differential scanning calorimetry, and X-ray diffraction measurements to examine their morphology (fiber diameter distribution, specific surface area, and total pore volume), composition, drug-loading efficiency, and physical state. An HPLC-UV method was optimized and validated to quantify in vitro PTX release into PBS. The results showed that the addition of PEG into PLA fibers promoted the release of higher amounts of hydrophobic PTX over prolonged time periods compared to fibers without PEG. An in vitro cell assay demonstrated the biocompatibility of PLA/PEG fibrous materials and showed significant cytotoxicity of PTX-loaded PLA/PEG fibers against a human fibrosarcoma HT1080 cell line. The chick chorioallantoic membrane assay proved that PTX-loaded fibers exhibited antiangiogenic activity, with a pronounced effect in the case of the PEG-containing fibers. In vivo evaluation of PTX-loaded PLA/PEG fibers in a human fibrosarcoma recurrence model showed statistically significant inhibition in tumor incidence and growth after primary tumor resection compared to other treatment groups.
- MeSH
- buněčná smrt účinky léků MeSH
- difrakce rentgenového záření MeSH
- inhibitory angiogeneze farmakologie MeSH
- kur domácí MeSH
- lidé MeSH
- lokální recidiva nádoru patologie prevence a kontrola MeSH
- myši nahé MeSH
- nádorové buněčné linie MeSH
- nanovlákna chemie ultrastruktura MeSH
- nosiče léků chemie MeSH
- paclitaxel farmakologie MeSH
- polyestery chemie MeSH
- polyethylenglykoly chemie MeSH
- tělesná hmotnost MeSH
- teplota MeSH
- tumor burden účinky léků MeSH
- uvolňování léčiv * MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Ritonavir (RIT) is a widely used antiviral drug that acts as an HIV protease inhibitor with emerging potential in anticancer therapies. RIT causes inhibition of P-glycoprotein, which plays an important role in multidrug resistance (MDR) in cancer cells when overexpressed. Moreover, RIT causes mitochondrial dysfunction, leading to decreased ATP production and reduction of caveolin I expression, which can affect cell migration and tumor progression. To increase its direct antitumor activity, decrease severe side effects induced by the use of free RIT and improve its pharmacokinetics, ritonavir 5-methyl-4-oxohexanoate (RTV) was synthesized and conjugated to a tumor-targeted polymer carrier based on a N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer. Here we demonstrated that polymer-bound RTV enhanced the internalization of polymer-RTV conjugates, differing in RTV content from 4 to 15 wt%, in HeLa cancer cells compared with polymer without RTV. The most efficient influx and internalization properties were determined for the polymer conjugate bearing 11 wt% of RTV. This conjugate was internalized by cells using both caveolin- and clathrin-dependent endocytic pathways in contrast to the RTV-free polymer, which was preferentially internalized only by clathrin-mediated endocytosis. Moreover, we found the co-localization of the RTV-conjugate with mitochondria and a significant decrease of ATP production in treated cells. Thus, the impact on mitochondrial mechanism can influence the function of ATP-dependent P-glycoprotein and also the cell viability of MDR cancer cells. Overall, this study demonstrated that the polymer-RTV conjugate is a promising polymer-based nanotherapeutic, suitable for antitumor combination therapy with other anticancer drugs and a potential mitochondrial drug delivery system.
- MeSH
- adenosintrifosfát biosyntéza MeSH
- antitumorózní látky aplikace a dávkování chemie MeSH
- chemorezistence účinky léků MeSH
- endocytóza účinky léků MeSH
- HeLa buňky MeSH
- kaveolin 1 biosyntéza genetika MeSH
- klathrin farmakologie MeSH
- koncentrace vodíkových iontů MeSH
- lidé MeSH
- methakryláty chemie MeSH
- nanostruktury chemie MeSH
- P-glykoprotein účinky léků metabolismus MeSH
- polymery MeSH
- ritonavir aplikace a dávkování analogy a deriváty chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Local application of anticancer agents prolongs the presence time and increases the concentration of drug in the target place and therefore may reduce serious side effects compared to drug systemic administration. The preparation of fibrous materials of polylactide (PLA) and polyethylene glycol (PEG) loaded with paclitaxel (PTX, 1 or 10 wt%) is presented. Scanning electron microscopy proves that PTX is homogeneously incorporated into the fibers. The addition of PEG of various molecular weights (6, 20, or 35 kDa) ensures the release of significantly higher amounts of hydrophobic PTX in a prolonged release time compared to the fibers containing PTX only. Present PLA-PEG fibrous carriers can serve as a drug depot for PTX since they exhibit significant toxicity for cancer cell lines in several-day experiment. They are promising for local recurrence therapy, where the initial release is efficient to kill tumor cells and continued release can prevent their subsequent proliferation.
- MeSH
- antitumorózní látky * chemie farmakokinetika farmakologie MeSH
- léky s prodlouženým účinkem chemie farmakokinetika farmakologie MeSH
- lidé MeSH
- MFC-7 buňky MeSH
- nádory farmakoterapie metabolismus patologie MeSH
- nosiče léků * chemie farmakokinetika farmakologie MeSH
- paclitaxel * chemie farmakokinetika farmakologie MeSH
- polyestery * chemie farmakokinetika farmakologie MeSH
- polyethylenglykoly * chemie farmakokinetika farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The incidence of tick-borne diseases caused by Borrelia burgdorferi sensu lato, Anaplasma phagocytophilum and Rickettsia spp. has been rising in Europe in recent decades. Early pre-assessment of acarological hazard still represents a complex challenge. The aim of this study was to model Ixodes ricinus questing nymph density and its infection rate with B. burgdorferi s.l., A. phagocytophilum and Rickettsia spp. in five European countries (Italy, Germany, Czech Republic, Slovakia, Hungary) in various land cover types differing in use and anthropisation (agricultural, urban and natural) with climatic and environmental factors (Normalized Difference Vegetation Index (NDVI), Normalized Difference Water Index (NDWI), Land Surface Temperature (LST) and precipitation). We show that the relative abundance of questing nymphs was significantly associated with climatic conditions, such as higher values of NDVI recorded in the sampling period, while no differences were observed among land use categories. However, the density of infected nymphs (DIN) also depended on the pathogen considered and land use. These results contribute to a better understanding of the variation in acarological hazard for Ixodes ricinus transmitted pathogens in Central Europe and provide the basis for more focused ecological studies aimed at assessing the effect of land use in different sites on tick-host pathogens interaction.
- MeSH
- Anaplasma phagocytophilum růst a vývoj MeSH
- Borrelia burgdorferi růst a vývoj MeSH
- časoprostorová analýza * MeSH
- gramnegativní bakterie růst a vývoj MeSH
- klíště mikrobiologie MeSH
- nymfa MeSH
- podnebí * MeSH
- Rickettsia růst a vývoj MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Evropa MeSH
Inflammation is a vital defense mechanism of living organisms. However, persistent and chronic inflammation may lead to severe pathological processes and evolve into various chronic inflammatory diseases (CID), e.g. rheumatoid arthritis, multiple sclerosis, multiple sclerosis, systemic lupus erythematosus or inflammatory bowel diseases, or certain types of cancer. Their current treatment usually does not lead to complete remission. The application of nanotherapeutics may significantly improve CID treatment, since their accumulation in inflamed tissues has been described and is referred to as extravasation through leaky vasculature and subsequent inflammatory cell-mediated sequestration (ELVIS). Among nanotherapeutics, water-soluble polymer-drug conjugates may be highly advantageous in CID treatment due to the possibility of their passive and active targeting to the inflammation site and controlled release of active agents once there. The polymer-drug conjugate consists of a hydrophilic biocompatible polymer backbone along which the drug molecules are covalently attached via a biodegradable linker that enables controlled drug release. Their active targeting or bio-imaging can be achieved by introducing the cell-specific targeting moiety or imaging agents into the polymer conjugate. Here, we review the relationship between polymer conjugates and inflammation, including the benefits of the application of polymer conjugates in inflammation treatment, the anti-inflammatory activity of polymer drug conjugates and potential polymer-promoted inflammation and immunogenicity.
- MeSH
- antiflogistika aplikace a dávkování chemie metabolismus MeSH
- idiopatické střevní záněty farmakoterapie metabolismus MeSH
- lidé MeSH
- nádory farmakoterapie metabolismus MeSH
- polymery aplikace a dávkování chemie metabolismus MeSH
- revmatoidní artritida farmakoterapie metabolismus MeSH
- výsledek terapie MeSH
- zánět farmakoterapie metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Cell-penetrating compounds are substances that enhance the cellular uptake of various molecular cargoes that do not easily cross the cellular membrane. The majority of cell-penetrating compounds described in the literature are cell-penetrating peptides (CPPs). This review summarizes the various structural types of cell-penetrating compounds, with the main focus on CPPs. The authors present a brief overview of the history of CPPs, discuss the various types of conjugation of CPPs to biologically active cargoes intended for cell internalization, examine the cell-entry mechanisms of CPPs, and report on the applications of CPPs in research and in preclinical and clinical studies.
- MeSH
- buněčná membrána účinky léků metabolismus MeSH
- endocytóza účinky léků fyziologie MeSH
- lidé MeSH
- penetrační peptidy aplikace a dávkování genetika metabolismus MeSH
- sekvence aminokyselin MeSH
- systémy cílené aplikace léků metody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
A conceptually new bimodal immunoradiotherapy treatment was demonstrated using thermoresponsive polymer β-glucan-graft-poly(2-isopropyl-2-oxazoline-co-2-butyl-2-oxazoline) bearing complexes of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid with yttrium-90(III) at the graft ends. The behavior of this thermoresponsive polymer in aqueous solutions was studied, and it showed the appropriate cloud point temperature for brachytherapy applications. The polymer was tested in vitro, and it exhibited nontoxicity and active uptake into cancer cells and macrophages with colocalization in the lysosomes and macrophagosomes. Moreover, the observed oxidative burst response of the leukocytes established the immunostimulatory properties of the polymer, which were also studied in vivo after injection into the thigh muscles of healthy mice. The subsequent histological evaluation revealed the extensive immune activation reactions at the site of injection. Furthermore, the production of tumor necrosis factor α induced by the prepared polymer was observed in vitro, denoting the optimistic prognosis of the treatment. The biodistribution study in vivo indicated the formation of the polymer depot, which was gradually degraded and excluded from the body. The radiolabeled polymer was used during in vivo antitumor efficiency experiments on mice with EL4 lymphoma. The immunoradiotherapy group (treated with the radiolabeled polymer) demonstrated the complete inhibition of tumor growth during the beginning of the treatment. Moreover, 7 of the 15 mice were completely cured in this group, while the others exhibited significantly prolonged survival time compared to the control group. The in vivo experiments indicated the considerable synergistic effect of using immunoradiotherapy compared to separately using immunotherapy or radiotherapy.
- MeSH
- antibakteriální látky chemická syntéza farmakologie MeSH
- antitumorózní látky chemická syntéza farmakologie terapeutické užití MeSH
- aza sloučeniny chemie MeSH
- beta-glukany chemie MeSH
- brachyterapie metody MeSH
- heterocyklické sloučeniny monocyklické chemie MeSH
- imunitní systém účinky léků MeSH
- komplexní sloučeniny chemie MeSH
- leukocyty účinky léků metabolismus MeSH
- lidé MeSH
- myši inbrední C57BL MeSH
- nádorové buněčné linie MeSH
- oxazoly chemie MeSH
- oxidace-redukce MeSH
- polymery chemie MeSH
- radioimunoterapie metody MeSH
- radioizotopy ytria chemie MeSH
- Staphylococcus aureus účinky léků MeSH
- teplota MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: West Nile virus (WNV) is currently the most important mosquito-borne pathogen spreading in Europe. Data on overwintering of WNV in mosquitoes are crucial for understanding WNV circulation in Europe; nonetheless, such data were not available so far. RESULTS: A total of 28,287 hibernating mosquitoes [27,872 Culex pipiens, 73 Anopheles maculipennis (sensu lato), and 342 Culiseta annulata], caught in February or March between 2011 and 2017 in a WNV-endemic region of South Moravia, Czech Republic, were screened for the presence of WNV RNA. No WNV positive pools were found from 2011 to 2016, while lineage 2 WNV RNA was detected in three pools of Culex pipens mosquitoes collected in 2017 at two study sites. CONCLUSIONS: To the best of our knowledge, this is the first record of WNV RNA in overwintering mosquitoes in Europe. The data support the hypothesis of WNV persistence in mosquitoes throughout the winter season in Europe.
- MeSH
- Culicidae virologie MeSH
- hmyz - vektory virologie MeSH
- lidé MeSH
- roční období MeSH
- virus západního Nilu genetika izolace a purifikace fyziologie MeSH
- západonilská horečka epidemiologie přenos virologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Evropa epidemiologie MeSH
