submicronization
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The effect of particle size on bioavailability of 9 different formulations with cyclosporine A was studied. A common feature of all the formulations was the ability to form submicron dispersions under dilution. The composition of individual formulations was chosen in such a way that they were based on same or similar excipients. For each formulation, pharmacokinetic study was carried out in beagle dogs. On groups of 10 dogs, the average AUC was evaluated. Particle size of formulations under dilution in water was measured by laser scattering method. According to the results of particle size measurement, the formulations were sorted out into groups of similar particle size distribution by use of two methods of multivariate statistical analysis. The average AUC within groups and between-groups was compared, and the effect of particle size on bioavailability was evaluated.
- MeSH
- biologická dostupnost MeSH
- cyklosporin aplikace a dávkování chemie farmakokinetika MeSH
- imunosupresiva aplikace a dávkování chemie farmakokinetika MeSH
- lékové transportní systémy * MeSH
- psi MeSH
- velikost částic MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- psi MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
A unique composite nanodiamond-based porous material with a hierarchically-organized submicron-nano-structure was constructed for potential bone tissue engineering. This material consisted of submicron fibers prepared by electrospinning of silicon oxide (SiOx), which were oxygen-terminated (O-SiOx) and were hermetically coated with nanocrystalline diamond (NCD) films. The NCD films were then terminated with hydrogen (H-NCD) or oxygen (O-NCD). The materials were tested as substrates for the adhesion, growth and osteogenic differentiation of human osteoblast-like Saos-2 cells. The number and the spreading area of the initially adhered cells, their growth rate during 7 days after seeding and the activity of alkaline phosphatase (ALP) were significantly higher on the NCD-coated samples than on the uncoated O-SiOx samples. In addition, the concentration of type I collagen was significantly higher in the cells on the O-NCD-coated samples than on the bare O-SiOx samples. The observed differences could be attributed to the tunable wettability of NCD and to the more appropriate surface morphology of the NCD-coated samples in contrast to the less stable, rapidly eroding bare SiOx surface. The H-NCD coatings and the O-NCD coatings both promoted similar initial adhesion of Saos-2 cells, but the subsequent cell proliferation activity was higher on the O-NCD-coated samples. The concentration of beta-actin, vinculin, type I collagen and alkaline phosphatase (ALP), the ALP activity, and also the calcium deposition tended to be higher in the cells on the O-NCD-coated samples than on the H-NCD-coated samples, although these differences did not reach statistical significance. The improved cell performance on the O-NCD-coated samples could be attributed to higher wettability of these samples (water drop contact angle less than 10°), while the H-NCD-coated samples were hydrophobic (contact angle >70°). NCD-coated porous SiOx meshes can therefore be considered as appropriate scaffolds for bone tissue engineering, particularly those with an O-terminated NCD coating.
- MeSH
- biokompatibilní potahované materiály farmakologie MeSH
- buněčná adheze MeSH
- buněčná diferenciace MeSH
- diamant * MeSH
- lidé MeSH
- osteoblasty MeSH
- osteogeneze * MeSH
- proliferace buněk MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
In intravenous immunoglobulins (IVIG), and some other immunoglobulin products, protein particles have been implicated in adverse events. Role and mechanisms of immunoglobulin particles in vascular adverse effects of blood components and manufactured biologics have not been elucidated. We have developed a model of spherical silica microparticles (SiMPs) of distinct sizes 200-2000 nm coated with different IVIG- or albumin (HSA)-coronas and investigated their effects on cultured human umbilical vein endothelial cells (HUVEC). IVIG products (1-20 mg/mL), bare SiMPs or SiMPs with IVIG-corona, did not display significant toxicity to unstimulated HUVEC. In contrast, in TNFα-stimulated HUVEC, IVIG-SiMPs induced decrease of HUVEC viability compared to HSA-SiMPs, while no toxicity of soluble IVIG was observed. 200 nm IVIG-SiMPs after 24 h treatment further increased ICAM1 (intercellular adhesion molecule 1) and tissue factor surface expression, apoptosis, mammalian target of rapamacin (mTOR)-dependent activation of autophagy, and release of extracellular vesicles, positive for mitophagy markers. Toxic effects of IVIG-SiMPs were most prominent for 200 nm SiMPs and decreased with larger SiMP size. Using blocking antibodies, toxicity of IVIG-SiMPs was found dependent on FcγRII receptor expression on HUVEC, which increased after TNFα-stimulation. Similar results were observed with different IVIG products and research grade IgG preparations. In conclusion, submicron particles with immunoglobulin corona induced size-dependent toxicity in TNFα-stimulated HUVEC via FcγRII receptors, associated with apoptosis and mTOR-dependent activation of autophagy. Testing of IVIG toxicity in endothelial cells prestimulated with proinflammatory cytokines is relevant to clinical conditions. Our results warrant further studies on endothelial toxicity of sub-visible immunoglobulin particles.
- MeSH
- apoptóza účinky léků MeSH
- autofagie * účinky léků MeSH
- endoteliální buňky pupečníkové žíly (lidské) * účinky léků metabolismus MeSH
- intravenózní imunoglobuliny * MeSH
- lidé MeSH
- mezibuněčná adhezivní molekula-1 metabolismus MeSH
- oxid křemičitý chemie toxicita MeSH
- proteinová korona metabolismus MeSH
- receptory IgG * metabolismus MeSH
- TNF-alfa * metabolismus MeSH
- TOR serin-threoninkinasy metabolismus MeSH
- velikost částic MeSH
- viabilita buněk účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Graphical Abstract.
- MeSH
- rentgenové záření MeSH
- tomografie * MeSH
- velikost částic MeSH
- Publikační typ
- časopisecké články MeSH
We analyzed the association of particle number and PM(2.5) concentrations with mortality and cardiorespiratory hospital admissions in Prague. Number concentrations of submicron particles in the range of 15-487 nm were measured continuously at a central site in 2006. The particle number concentrations were integrated into four groups with count median diameters of 31 (NC(31)), 128 (NC(128)), and 346 nm (NC(346)). The total number concentration of submicron particles 15-487 nm (NC(tot)) was also constructed. The studied health outcomes were the daily hospital admissions due to cardiovascular and respiratory diseases and daily cardiovascular and respiratory mortality and the total mortality. The Poisson regression was used for data analysis. The strongest association was found for the accumulation mode particles (NC(346)) (RR 1.164, 95% CI: 1.052-1.287 for cardiovascular and 1.334, 95% CI: 1.126-1.579 for respiratory admissions for a 7-day moving average for 1000 particles per 1 cm(3) increase). Reasonable association between both the cardiovascular and respiratory admissions and NC(346) was also found for lag 0, lag 1, lag 2 (not for respiratory admissions), and the 4-day moving average. For NC(128) and NC(tot), the association was also significant for both cardiovascular and respiratory admissions at lag 0, lag 1, and lag 2 (not for respiratory admissions) for the 4-day and 7-day moving average. The association between the PM(2.5) and daily cardiovascular hospital admissions was significant at 2-day lag and for a 4-day average. Positive association with respiratory admissions was significant only for a 7-day average. No association was found between the studied air pollution variables and daily mortality.
- MeSH
- kardiovaskulární nemoci mortalita MeSH
- látky znečišťující vzduch škodlivé účinky MeSH
- lidé MeSH
- nemocnice MeSH
- pevné částice škodlivé účinky MeSH
- poruchy dýchání mortalita MeSH
- velikost částic MeSH
- vystavení vlivu životního prostředí analýza MeSH
- zdraví ve městech MeSH
- znečištění ovzduší analýza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
Verification of a simple technique for monitoring of aerosol particles in dental surgery as well as determination of particle concentrations and size distribution were performed. It was found that the main source of aerosol particles in the surgery hours is teeth drilling, grinding and resuspension of particles in cleaning the surgery. The particle concentration increased 1.5 times during the surgery and the total particle concentrations during surgery hours were by 30 % higher compared with the background values. The concentration increase was pronounced in all particle size fractions, the largest for particles < 1µm. Comparing the results of mass and number concentrations of submicron fraction, it was found out that the individual surgery is capable of producing particles < 0.375 µm.
Background: Antimicrobial submicrometer particles are being studied as promising interventions against a wide range of skin conditions, such as fungal or bacterial infections. Aims: To submicronize chloroxine, the crystalline compound 5,7-dichloro-8-hydroxyquinoline, by nanoprecipitation and characterize the resulting assemblies. Methods: The chloroxine particles were stabilized by a nonionic surfactant and were studied by a broth microdilution assay against 20 medically important bacteria and fungi. The intervention was studied using a murine model of skin irritation. Results & conclusion: Chloroxine nanoparticles with a diameter of 600-800 nm exhibit good tolerability in terms of skin irritation in vivo and good antimicrobial activity. Thus, the fabricated formulation shows great promise for interventions for both cutaneous infection control and prophylaxis.
Mucosal surfaces are the first mechanical barrier preventing the entry of foreign particles into the organism. The study addresses the detection and analysis of metal-based solid particles in cytological mucus samples from the surface of human hypertrophic tissue in the inferior nasal turbinates in patients diagnosed with chronic rhinitis. Solid particles were characterized by scanning electron microscopy and Raman microspectroscopy; all the biological samples were also subjected to vibration magnetometry. Since the upper airways are the first part of the respiratory tract, which is exposed to inhaled particles, it can be assumed that inhaled particles may be partially deposited in this region. Scanning electron microscopy revealed the presence of metal-based solid particles/clusters in the majority of the analysed cytological mucus samples and also in hypertrophic tissues; in all groups, the particles were of submicron size. Raman microspectroscopy detected the presence of particles/clusters based on amorphous carbon, graphite, calcium carbonate, anatase and barite only in the hypertrophic tissue. The obtained results show that the composition of some of the solid particles (i.e. Ba, Zn, Fe and Ti) detected in the mucus from the surface of the hypertrophic tissues resembled the particles found in the hypertrophic tissue itself. It can be assumed that after the capture of the inhaled particles by the mucus, they penetrate into the deeper layers of tissue.
Settled road dust was examined to detect the presence of non-airborne submicron and nano-sized iron-based particles and to characterize these particles. Samples were collected from a road surface near a busy road junction in the city of Ostrava, Czech Republic, once a month from March to October. The eight collected samples were subjected to a combination of experimental techniques including elemental analysis, Raman microspectroscopy, scanning electron microscopy (SEM) analysis, and magnetometry. The data thereby obtained confirmed the presence of non-agglomerated spherical nano-sized iron-based particles, with average sizes ranging from 2 down to 490 nm. There are several sources in road traffic which generate road dust particles, including exhaust and non-exhaust processes. Some of them (e.g., brake wear) produce iron as the dominant metallic element. Raman microspectroscopy revealed forms of iron (mainly as oxides, Fe2O3, and mixtures of Fe2O3 and Fe3O4). Moreover, Fe3O4 was also detected in samples of human tissues from the upper and lower respiratory tract. In view of the fact that no agglomeration of those particles was found by SEM, it is supposed that these particles may be easily resuspended and represent a risk to human health due to inhalation exposure, as proved by the detection of particles with similar morphology and phase composition in human tissues.
- MeSH
- dýchací soustava účinky léků metabolismus MeSH
- inhalační expozice analýza MeSH
- lidé MeSH
- monitorování životního prostředí metody MeSH
- oxid železnato-železitý analýza MeSH
- prach analýza MeSH
- velikost částic MeSH
- velkoměsta MeSH
- výfukové emise vozidel analýza MeSH
- železité sloučeniny analýza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
- velkoměsta MeSH
Boron-doped nanocrystalline diamond (BNCD) films exhibit outstanding electrochemical properties that make them very attractive for the fabrication of electrodes for novel neural interfaces and prosthetics. In these devices, the physicochemical properties of the electrode materials are critical to ensure an efficient long-term performance. The aim of this study was to investigate the relative contribution of topography and doping to the biological performance of BNCD films. For this purpose, undoped and boron-doped NCD films were deposited on low roughness (LR) and high roughness (HR) substrates, which were studied in vitro by means of protein adsorption and fibroblast growth assays. Our results show that BNCD films significantly reduce the adsorption of serum proteins, mostly on the LR substrates. As compared to fibroblasts cultured on LR BNCD films, cells grown on the HR BNCD films showed significantly reduced adhesion and lower growth rates. The mean length of fibronectin fibrils deposited by the cells was significantly increased in the BNCD coated substrates, mainly in the LR surfaces. Overall, the largest influence on protein adsorption, cell adhesion, proliferation, and fibronectin deposition was due to the underlying sub-micron topography, with little or no influence of boron doping. In perspective, BNCD films displaying surface roughness in the submicron range may be used as a strategy to reduce the fibroblast growth on the surface of neural electrodes.
- MeSH
- 4-aminopyridin analogy a deriváty metabolismus MeSH
- aktiny fyziologie MeSH
- bor chemie MeSH
- buněčná adheze fyziologie MeSH
- diamant chemie MeSH
- fibroblasty fyziologie MeSH
- krevní proteiny chemie MeSH
- kultivované buňky MeSH
- lidé MeSH
- membrány umělé MeSH
- nanočástice * MeSH
- povrchové vlastnosti MeSH
- proliferace buněk MeSH
- testování materiálů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
