Pharmaceutical nanocrystals represent a promising new formulation that combines the benefits of bulk crystalline materials and colloidal nanoparticles. To be applied in vivo, nanocrystals must meet several criteria, namely colloidal stability in physiological media, non-toxicity to healthy cells, avoidance of macrophage clearance, and bioactivity in the target tissue. In the present work, curcumin, a naturally occurring poorly water-soluble molecule with a broad spectrum of bioactivity has been considered a candidate substance for preparing pharmaceutical nanocrystals. Curcumin nanocrystals in the size range of 40-90 nm were prepared by wet milling using the following combination of steric and ionic stabilizers: Tween 80, sodium dodecyl sulfate, Poloxamer 188, hydroxypropyl methylcellulose, phospholipids (with and without polyethylene glycol), and their combination. Nanocrystals stabilized by a combination of phospholipids enriched with polyethylene glycol proved to be the most successful in all evaluated criteria; they were colloidally stable in all media, exhibited low macrophage clearance, and proved non-toxic to healthy cells. This curcumin nanoformulation also exhibited outstanding anticancer potential comparable to commercially used cytostatics (IC50 = 73 μM; 24 h, HT-29 colorectal carcinoma cell line) which represents an improvement of several orders of magnitude when compared to previously studied curcumin formulations. This work shows that the preparation of phospholipid-stabilized nanocrystals allows for the conversion of poorly soluble compounds into a highly effective "solution-like" drug delivery system at pharmaceutically relevant drug concentrations.
- MeSH
- deriváty hypromelózy MeSH
- dodecylsíran sodný chemie MeSH
- fosfolipidy MeSH
- kurkumin * chemie farmakologie MeSH
- léčivé přípravky MeSH
- makrofágy MeSH
- nanočástice * chemie MeSH
- poloxamer chemie MeSH
- polyethylenglykoly chemie MeSH
- polysorbáty MeSH
- rozpustnost MeSH
- velikost částic MeSH
- voda MeSH
- Publikační typ
- časopisecké články MeSH
The organochlorine pesticides (OCPs) have raised concerns about being persistent and toxic to the environment. Phytoremediation techniques show promise for the revitalization of polluted soils. The current study focused on optimizing the phytoremediation potential of Miscanthus sinensis And. (M. sinensis), second-generation energy crop, by exploring two soil amendments: Tween 20 and activated carbon (AC). The results showed that when M. sinensis grew in OCP-polluted soil without amendments to it, the wide range of compounds, i.e., α-HCH, β-HCH, γ-HCH, 2.4-DDD, 4.4-DDE, 4.4-DDD, 4.4-DDT, aldrin, dieldrin, and endrin, was accumulated by the plant. The introduction of soil amendments improved the growth parameters of M. sinensis. The adding of Tween 20 enhanced the absorption and transmigration to aboveground biomass for some OCPs; i.e., for γ-HCH, the increase was by 1.2, for 4.4-DDE by 8.7 times; this effect was due to the reduction of the hydrophobicity which made pesticides more bioavailable for the plant. The adding of AC reduced OCPs absorption by plants, consequently, for γ-HCH by 2.1 times, 4.4-DDD by 20.5 times, 4.4-DDE by 1.4 times, 4.4-DDT by 8 times, α-HCH was not adsorbed at all, and decreased the translocation to the aboveground biomass: for 4.4-DDD by 31 times, 4.4-DDE by 2.8 times, and γ-HCH by 2 times; this effect was due to the decrease in the bioavailability of pesticides. Overall, the amendment of OCP-polluted soil by Tween 20 speeds the remediation process, and incorporation of AC permitted to produce the relatively clean biomass for energy.
Očkovanie proti COVID-19 patrí v súčasnosti k najdôležitejším témam na diskusiu. Aj vzhľadom k viacerým medializovaným informáciám o závažných alergických reakciách po očkovaní mRNA vakcínami v zahraničí sa na špecialistov v odbore klinická imunológia aalergológia obracajú pacienti s otázkou zhodnotenia miery rizika očkovania. Klinický imunológ a alergológ má zároveň kľúčové postavenie v diferenciálnej diagnostike anáslednom manažmente postvakcinačných reakcií. V nasledujúcom článku uvádzame aktuálne poznatky oočkovaní proti COVID-19 z pohľadu imunológa a alergiológa s odvolaním sa na bežné postupy vo vakcinológii a odporúčania odborných spoločností.
Vaccination against COVID-19 is currently one of the most important topics for discussion. Due to published information about severe allergic reactions after vaccination with mRNA vaccines abroad, specialists in the field of clinical immunology and allergology are frequently asked to assess the risk of vaccination. At the same time, clinical immunologist and allergist has akey role in the differential diagnosis and subsequent management of post-vaccination reactions. In the following article, we present current knowledge about vaccination against COVID-19 from the perspective of aclinical immunologist and allergist with reference to standard vaccination recommendations and guidelines of medical societies.
BACKGROUND: The absolute degree of protection from influenza vaccines in older adults has not been studied since 2001. This study aimed to show the clinical efficacy of an MF59-adjuvanted quadrivalent influenza vaccine (aQIV) in adults 65 years or older compared with adults not vaccinated to prevent influenza. METHODS: We did a randomised, stratified, observer-blind, controlled, multicentre, phase 3 study at 89 sites in 12 countries in 2016-17 northern hemisphere and 2017 southern hemisphere influenza seasons. We enrolled community-dwelling male and female adults aged 65 years and older who were healthy or had comorbidities that increased their risk of influenza complications. We stratified eligible participants by age (cohorts 65-74 years and ≥75 years) and risk of influenza complications (high and low) and randomly assigned them (1:1) via an interactive response technology to receive either aQIV or a non-influenza comparator vaccine. We masked participants and outcome assessors to the administered vaccine. Personnel administering the vaccines did not participate in endpoint assessment. The primary outcome was absolute vaccine efficacy assessed by RT-PCR-confirmed influenza due to any influenza strain in the overall study population (full analysis set) from day 21 to 180 or the end of the influenza season. Vaccine efficacy was calculated on the basis of a Cox proportional hazard regression model for time to first occurrence of RT-PCR-confirmed influenza due to any strain of influenza. Safety outcomes were assessed in the overall study population. This trial was registered with ClinicalTrials.gov, NCT02587221. FINDINGS: Northern hemisphere enrolment occurred between Sept 30, 2016, and Feb 28, 2017, and southern hemisphere enrolment between May 26, 2017, and 30 June 30, 2017. aQIV was administered to 3381 participants, who subsequently had 122 (3·6%) RT-PCR-confirmed influenza cases, and the comparator was administered to 3380 participants, who subsequently had 151 (4·5%) influenza cases. The majority, 214 (78·4%) of 273, were caused by influenza A H3N2. Most antigenically characterised isolates were mismatched to the vaccine strain (118 [85%] of 139). Vaccine efficacy was 19·8% (multiplicity-adjusted 95% CI -5·3 to 38·9) against all influenza and 49·9% (-24·0 to 79·8) against antigenically matched strains, when the protocol definition of influenza-like illness was used. The most common local solicited adverse event was injection site pain, reported by 102 (16·3%) of 624 participants in the aQIV group and 71 (11·2%) of 632 of participants in the comparator group. Deaths were evenly distributed; none were considered related to study vaccines. The safety profile for aQIV was similar to previously reported trials. INTERPRETATION: The prespecified criterion for showing the efficacy of aQIV in older adults was not met during the influenza seasons with high amounts of vaccine strain mismatch. Vaccine efficacy was higher against influenza cases associated with higher fever, which represent more clinically significant disease. FUNDING: Seqirus UK.
- MeSH
- adjuvancia imunologická aplikace a dávkování MeSH
- chřipka lidská prevence a kontrola MeSH
- lidé MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- polysorbáty * MeSH
- rizikové faktory MeSH
- roční období * MeSH
- senioři MeSH
- skvalen * MeSH
- vakcíny proti chřipce aplikace a dávkování MeSH
- virus chřipky A, podtyp H3N2 imunologie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
We have employed a model system, inspired by SNARE proteins, to facilitate membrane fusion between Giant Unilamellar Vesicles (GUVs) and Large Unilamellar Vesicles (LUVs) under physiological conditions. In this system, two synthetic lipopeptide constructs comprising the coiled-coil heterodimer-forming peptides K4, (KIAALKE)4, or E4, (EIAALEK)4, a PEG spacer of variable length, and a cholesterol moiety to anchor the peptides into the liposome membrane replace the natural SNARE proteins. GUVs are functionalized with one of the lipopeptide constructs and the fusion process is triggered by adding LUVs bearing the complementary lipopeptide. Dual-colour time lapse fluorescence microscopy was used to visualize lipid- and content-mixing. Using conventional confocal microscopy, lipid mixing was observed on the lipid bilayer of individual GUVs. In addition to lipid-mixing, content-mixing assays showed a low efficiency due to clustering of K4-functionalized LUVs on the GUVs target membranes. We showed that, through the use of the non-ionic surfactant Tween 20, content-mixing between GUVs and LUVs could be improved, meaning this system has the potential to be employed for drug delivery in biological systems.
- MeSH
- barva MeSH
- cholesterol chemie MeSH
- dimerizace MeSH
- fluorescenční mikroskopie metody MeSH
- fluorescenční spektrometrie MeSH
- fúze membrán * MeSH
- konfokální mikroskopie MeSH
- lipidy chemie MeSH
- lipopeptidy chemie MeSH
- peptidy chemie MeSH
- polysorbáty chemie MeSH
- rezonanční přenos fluorescenční energie MeSH
- unilamelární lipozómy chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Despite the increasing interest in pharmaceutical use of mesoporous silica, there is still only limited knowledge on mechanisms of pore loading and subsequent drug desorption and release. Hence the aim of this work was to address the mechanistic aspects of drug loading into the mesoporous silica pores and to minimise the risk of pore clogging. Hydrophilic solvents (polysorbate 20 and polyethylene glycol 200) with high dissolving capacity for the model drug celecoxib were studied for their surface tension as well as dynamic viscosity by considering hydration. As an innovation in liquisolid systems preparation, a rather simple drug loading method on a mesoporous carrier was introduced by using semi-volatile solvent mixtures. Fast liquid loading into the pores was achieved due to the lowered viscosity and surface tension of the whole solvent system. Drug release kinetics suggested that lipid-based formulations belonging to class IV of Lipid Formulation Classification System may exhibit a lower risk of incomplete desorption from a carrier. The utilisation of volatile solvents during preparation had no negative impact on the liquisolid systems' dissolution behaviour. All prepared formulations showed similar significantly faster dissolution profiles compared to the physical mixture. The novel approach has potential to promote liquisolid applications in pharmaceutics.
- MeSH
- chemie farmaceutická metody MeSH
- diferenciální skenovací kalorimetrie metody MeSH
- farmaceutická technologie metody MeSH
- hydrofobní a hydrofilní interakce MeSH
- kinetika MeSH
- léčivé přípravky chemie MeSH
- lipidy chemie MeSH
- nosiče léků chemie MeSH
- oxid křemičitý chemie MeSH
- polysorbáty chemie MeSH
- propylenglykol chemie MeSH
- rozpouštědla chemie MeSH
- rozpustnost účinky léků MeSH
- tablety chemie MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: The aim of this study was to evaluate the rate of contact sensitization to selected cosmetic allergens, i.e. ingredients of dental materials, in students of dental medicine and dental patients. METHODS: A total of 50 participants were included in the study: 40 students of dental medicine exposed to the studied allergens during the course of practical education; and 10 randomly selected dental patients without occupational exposure to the investigated substances served as a control group. All of them were patch-tested with colophonium, myroxylon pereirae resin, paraben mix, fragrance mix I, isopropyl myristate, triclosan, polysorbate 80, compositae mix II, and hydroperoxides of limonene. RESULTS: The sensitization rates for colophonium and polysorbate 80 were the highest. For the group of dental students, we established significantly higher sensitization rate for colophonium compared to the ones for myroxylon pereirae resin and hydroperoxides of limonene (χ2 = 4.93; p = 0.026), paraben mix (χ2 = 3.6; p = 0.05), isopropyl myristate (χ2 = 6.56; p = 0.01), and triclosan (χ2 = 8.5; p < 0.001); and to polysorbate 80 compared to the ones for myroxylon pereirae resin and hydroperoxides of limonene (χ2 = 3.97; p = 0.046), isopropyl myristate (χ2 = 5.47; p = 0.02) and triclosan (χ2 = 7.34; p = 0.007). Significantly increased concomitant sensitization rate to compositae mix and to hydroperoxides of limonene was established (χ2 = 12.55; p < 0.001). Generally, the incidence of concomitant sensitization to the studied allergens in the whole studied population was high. CONCLUSIONS: Colophonium and polysorbate 80 could be outlined as sensitizers of paramount importance for both dental students and dental patients. We consider the major importance of exposure to colophonium during the course of practical education in dentistry for the onset of the sensitization. Sensitization to compositae mix was observed only among dental students. We consider the leading role of consumer exposure for the onset of the sensitization to triclosan and to hydroperoxides of limonene. Unexpected and unreported reactions of concomitant sensitization were observed.
- MeSH
- alergická kontaktní dermatitida epidemiologie etiologie imunologie MeSH
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- náplasťové testy metody MeSH
- parfém škodlivé účinky MeSH
- pilotní projekty MeSH
- polysorbáty škodlivé účinky MeSH
- pracovní expozice škodlivé účinky MeSH
- rostlinné pryskyřice škodlivé účinky MeSH
- studenti stomatologie MeSH
- studie případů a kontrol MeSH
- zubní materiály toxicita MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- Publikační typ
- časopisecké články MeSH
Unknown impurities were identified in ibuprofen (IBU) soft gelatin capsules (SGCs) during long-term stability testing by a UHPLC method with UV detection and its chemical formula was determined using high resolution/accurate mass (HRAM) LC-MS. Reference standards of the impurities were subsequently synthesized, isolated by semi-preparative HPLC and characterized using HRAM LC-MS, NMR and IR. Two impurities were formed by esterification of IBU with polyethylene glycol (PEG), which is used as a fill of the SGCs, and were identified as IBU-PEG monoester and IBU-PEG diester. Two other degradants arised from reaction of IBU with sorbitol and sorbitan, which are components of the shell and serves as plasticizers. Thus, IBU sorbitol monoester (IBU-sorbitol) and IBU sorbitan monoester (IBU-sorbitan ester) were identified. An UHPLC method was further optimized in order to separate, selectively detect and quantify the degradation products in IBU SGCs.
Formaldehyd, jako chemická látka, slouží k inaktivaci bakterií, virů nebo odstranění toxicity bakteriálních toxinů použitých při výrobě vakcín. Ve vakcíně zůstává jako reziduální látka z výrobního procesu. Nejčastěji se používá u vakcín s difterickým, tetanickým nebo pertusovým anatoxinem. Formaldehyd se běžně nachází v krevním oběhu člověka (2,6 mg/l). V Evropě je povolené maximální množství formaldehydu ve vakcíně 0,2 mg/ml. Podle výsledků farmakokinetického modelování dochází k eliminaci formaldehydu z místa intramuskulárního vpichu do 30 minut po aplikaci a dosažení jeho koncentrace v tělních tekutinách < 1 % běžného endogenního množství v lidském těle. Dosud nebylo popsáno závažné poškození po očkování způsobené formaldehydem. Stabilizátory ve vakcínách jsou ponechány záměrně pro svůj efekt na kvalitu a stabilitu vakcíny po dobu použitelnosti. Jedná se zejména o cukry (sacharóza, laktóza), aminokyseliny (glycin, glutaman sodný), proteiny (želatina, lidský albumin). Stabilitu vakcín zajišťují také emulgátory - polysorbát 80. Bezpečnostní profil stabilizátorů ve vakcínách je dobrý. Ke klidu a eliminaci obav z očkování může přispět znalost obsahu a významu těchto látek ve vakcínách. Detailní uvádění složení vakcín a přítomnosti látek ve stopovém množství by mělo být součástí dostupných informací pro lékaře, ale i pro zájemce o očkování.
Formaldehyde is a chemical agent that is used to inactivate bacterium, viruses or detoxify bacterial toxins during vaccine manufacturing. It remains as manufacturing residual in vaccines. The most often use is in diphtheria, tetanus or pertussis toxoids vaccines. The usual level of formaldehyde in the blood of human is 2.6 mg/l. In Europe there is permitted a maximum level of formaldehyde 0.2 mg/ml. Pharmacokinetic model showed formaldehyde elimination from the site of intramuscular injection within 30 minutes and its concentration in blood/body water < 1% of usual level of endogenous formaldehyde in human. It has not been described severe damage caused with formaldehyde after immunization till now. Stabilizers in vaccines are left intentionally for their effect on the quality and stability of the vaccine for a period of application. These include sugars (sucrose, lactose), amino acids (glycine, sodium glutamate), proteins (gelatin, human albumin). Ensure the stability of the vaccine emulsifiers - polysorbate 80. The safety profile of stabilizers in vaccines remains good. Knowledge of the content and importance of these substances in vaccines can contribute to peace and eliminate the fear of vaccination. Detailed declaration of vaccine composition and the presence of substances in trace amounts should be part of the available information for physicians, but also for those interested in vaccination.
- Klíčová slova
- polysorbát 80 (Tween 80), stabilizátory,
- MeSH
- chemie farmaceutická MeSH
- farmaceutické pomocné látky normy škodlivé účinky MeSH
- formaldehyd * farmakokinetika krev normy škodlivé účinky MeSH
- injekce intramuskulární MeSH
- lidé MeSH
- polysorbáty škodlivé účinky toxicita MeSH
- pomocné látky * škodlivé účinky MeSH
- vakcíny * chemie škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
A potential delivery system has to be fabricated for crossing the blood–brain barrier (BBB) to reach the brain fluid for effective delivery of drugs for any neurological disorders. The present study is aimed for the delivery of donepezil through functionalized PNIPAM nanogel by overcoming the BBB using zebrafish model. We had synthesized the poly N-isopropyl acrylamide nanogels with 20 nm size for sustained drug release. The entrapment of donepezil in the nanogel was quantified as 87.5% by HPLC and its sustained drug release pattern was achieved at 37 °C using Janus green dye release assay. Acetylcholineesterase inhibition assay for the donepezil conjugated nanogel (DCN) has confirmed thermoresponsive drug release by obtaining the donepezil peak at 9.3 min retention time in HPLC. Swim behavior and heart beat rates were found to be biocompatible for the functionalized nanogel DCN in zebrafish. Histological analysis revealed increased pial surface in anterior telenchepalon region of zebrafish brain for the DCN administered fishes. DCN treated embryos exhibited minor developmental deformities above 5 μg/ml and thus confirmed its minimal toxicity and its therapeutic efficiency. This study may shed light on the development of neurospecific nanogel for targeted and sustained drug release to brain by crossing the blood–brain barrier.
- Klíčová slova
- PNIPAM,
- MeSH
- acetylcholinesterasa MeSH
- akrylové pryskyřice MeSH
- chemie farmaceutická MeSH
- dánio pruhované MeSH
- donepezil MeSH
- hematoencefalická bariéra * metabolismus MeSH
- indany farmakokinetika farmakologie MeSH
- kardiotoxicita etiologie MeSH
- modely u zvířat MeSH
- nanočástice MeSH
- nanotechnologie * MeSH
- PEG-DMA hydrogel chemická syntéza MeSH
- piperidiny farmakokinetika farmakologie MeSH
- polysorbáty MeSH
- systémy cílené aplikace léků * MeSH
- uvolňování léčiv MeSH
- velikost částic MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
