Enabling formulation(s)
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Současná efektivní antibiotická léčba vyžaduje moderní přístupy zaměřené na optimalizaci terapie a zpomalení růstu antimikrobiální rezistence. Klíčovým nástrojem v nemocnicích je koncept antimikrobiálního stewardshipu, který stojí na spolupráci v multidisciplinárních týmech složených z infektologů, mikrobiologů, klinických farmaceutů a epidemiologů. Tyto týmy se zaměřují na správnou volbu antibiotika a jeho dávkování, monitorování jeho účinnosti a minimalizaci nežádoucích účinků. Rozšiřující se možnosti v oblasti monitoringu a interpretace plazmatických koncentrací stále většího počtu antibiotik umožňují efektivně a bezpečně pracovat s dávkami a způsoby podání (prodloužené, kontinuální infuze) optimálními pro konkrétního pacienta, respektive umožňují personalizovaný přístup k farmakoterapii. Optimalizovat dávkování antibiotik pomáhá také využití moderních aplikačních pomůcek. V nemocničním prostředí ke zvýšení bezpečnosti vede rovněž elektronická parametrická ordinace, centralizovaná příprava a výdej antiinfektiv nemocniční lékárnou. V ambulantní sféře se rozšiřují možnosti prostřednictvím konceptu ambulantní parenterální antimikrobiální terapie, který snižuje riziko nozokomiálních infekcí a přináší komfort domácího prostředí pro pacienty. Jeho širšímu využití brání především nedostatečná oficiální stabilitní data antibiotických přípravků, ale i administrativní a finanční bariéry spojené se zaváděním tohoto inovativního konceptu do rutinní praxe.
The current effective antibiotic therapy requires modern approaches focused on optimizing treatment and slowing the growth of antimicrobial resistance. A key tool in hospitals is the concept of antimicrobial stewardship, which relies on collaboration in multidisciplinary teams composed of infectious disease specialists, microbiologists, clinical pharmacists, and epidemiologists. These teams focus on the correct choice of antibiotic and its dosage, monitoring its effectiveness and minimising adverse effects. Expanding possibilities in the field of monitoring and interpretation of plasma concentrations of an increasing number of antibiotics enable effective and safe optimization of dosing and administration methods (prolonged and continuous infusions) adjusted for individual patients, thereby allowing a personalized approach to pharmacotherapy. The optimization of antibiotic dosing is further supported using modern administration tools. In the hospital setting, electronic parametric prescribing, centralized preparation and dispensing of anti-infectives by the hospital pharmacy also leads to improved safety. In outpatient care, possibilities are expanding with the concept of outpatient parenteral antimicrobial therapy, which reduces the risk of nosocomial infections and provides the comfort of a home environment for patients. However, its broader use is hindered mainly by the lack of official stability data for antibiotic preparations, as well as administrative and financial barriers associated with integrating this innovative concept into routine practice.
In recent years, deep eutectic solvents (DESs) with their outstanding solubilization properties have emerged as strong candidates for oral enabling formulations of poorly soluble drugs. This study explores the use of drug-based therapeutic DESs (THEDESs) to solubilize a poorly soluble compound with the aim of providing a fixed-dose combination of two complementary therapeutic agents. Specifically, potential anticancer effects of ibuprofen (IBU) are harnessed in a novel type of THEDES to dissolve higher amounts of abiraterone acetate (AbAc), an antitumor agent. Four IBU-based combinations were studied: 1:4 M ratio with octanoic acid (OctA), 1:5 with nonanoic acid (NonA), 1:3 with decanoic acid (DeA) or 1:2 with dodecanoic acid (DoA). Fatty acids of different chain lengths were analyzed and discussed considering surface charge densities obtained via quantum chemistry. The THEDESs listed could apparently dissolve AbAc amounts up to 1311.0 ± 125.4 mg/g in IBU:OctA THEDES, 1151.7 ± 22.2 mg/g in IBU:NonA, 1160.4 ± 33.5 mg/g in IBU:DeA, and 231.3 ± 10.7 mg/g in IBU:DoA. In vitro dissolution of the simultaneously released drugs reached 37.8 ± 9.0 % to 64.2 ± 1.0 % for IBU and 5.0 ± 3.3 % to 19.4 ± 0.1 % for AbAc. This increased to between 60.4 ± 2.8 % and 79.4 ± 5.0 % of released IBU, and 23.6 ± 1.0 % to 57.3 ± 5.8 % of released AbAc, with 20 % (w/w) Tween 80 added to the formulations. This showed the significant potential of drug-containing THEDESs as solubilizing agents for poorly soluble drugs, in the form of fixed-dose combinations of synergistic APIs.
- MeSH
- abirateron * chemie aplikace a dávkování MeSH
- farmaceutická chemie metody MeSH
- fixní kombinace léků MeSH
- ibuprofen * chemie aplikace a dávkování MeSH
- mastné kyseliny chemie MeSH
- příprava léků metody MeSH
- protinádorové látky chemie aplikace a dávkování MeSH
- rozpouštědla * chemie MeSH
- rozpustnost * MeSH
- uvolňování léčiv MeSH
- Publikační typ
- časopisecké články MeSH
Východiska: V tradičním pojetí vnímání univerzit byl dlouhou dobu akcentován model první a druhé role. První role univerzit byla vždy spjata se samotným vzděláváním. Druhá role pak s vědecko-výzkumnou činností. Třetí role univerzit je dnes již zakotvena jako nedílná součást dlouhodobých záměrů většiny univerzit. Hlavní myšlenkou je především skutečnost, že univerzity, fakulty a její parciální pracoviště by se neměly uzavírat do sebe samých, ale měly by zaujmout aktivní roli ve veřejném prostoru. V současnosti jedním z modelů naplňování třetí role je pojetí univerzity, která může být pojímána nebo se může profilovat jako podnikatelský subjekt – triple helix model. Tímto může docházet k větší propojenosti univerzit s aplikační a podnikatelskou praxí. Tato skutečnost následně umožňuje komercializovat výsledky vědecko-výzkumné činnosti, podílet se na pokrytí nákladových položek a případně generovat zisk konkrétních univerzitních pracovišť. Cíle: Cílem práce je představení konceptu Průmysl 4.0, jeho vliv a přesahy do oblasti práce a vzdělávání, včetně naplňování třetí role univerzit. V analytické části je cílem představit konkrétní příklady „dobré praxe“ v realizaci naplňování třetí role v rámci činnosti univerzitního vědeckotechnického parku a ve spolupráci s dalšími významnými univerzitními pracovišti v ČR a subjekty z podnikatelského prostředí. Závěry: Předložená práce naznačuje možnosti propojení univerzitního prostředí a vybraných pracovišť s podnikatelským prostředím na konkrétních příkladech dobré praxe. Jsou předloženy možnosti vzájemné spolupráce různých univerzitních pracovišť s komerční sférou, ve snaze naplňovat třetí roli univerzit v kontextu modelu triple helix.
Background: The traditional perception of universities has long emphasised the first and second role model. The first role of universities has always been linked to education itself. The second role has been linked to scientific research. The third role of universities is now embedded as an integral part of the long-term goals of most universities. Above all, the main idea is that universities, faculties and their departments should not be self-contained but should take an active role in the public sphere. Currently, one model for fulfilling the third role is the notion of a university that can be conceived or profile itself as a business entity - the triple helix model. This may lead to greater interconnection between universities and application and business practice. This in turn enables the commercialization of the results of scientific research activities, participation in cost recovery and possibly profit generation for specific university departments. Objective: The aim of the thesis is to introduce the concept of Industry 4.0, its impact and overlaps in the field of work and education, including the fulfilment of the third role of universities. In the analytical part, the aim is to present concrete examples of "good practice" in the implementation of the third role within the activities of the university science and technology park and in cooperation with other major universities in the Czech Republic and entities from the business environment. Conclusions: The presented work indicates the possibilities of linking the university environment and selected departments with the business environment on specific examples of good practice. The possibilities of mutual cooperation between different university departments and the commercial sphere are presented, in an attempt to fulfil the third role of universities in the context of the triple helix model.
Diagnostic work-up and risk stratification in patients with bladder cancer before and after treatment must be refined to optimize management and improve outcomes. MRI has been suggested as a non-invasive technique for bladder cancer staging and assessment of response to systemic therapy. The Vesical Imaging-Reporting And Data System (VI-RADS) was developed to standardize bladder MRI image acquisition, interpretation and reporting and enables accurate prediction of muscle-wall invasion of bladder cancer. MRI is available in many centres but is not yet recommended as a first-line test for bladder cancer owing to a lack of high-quality evidence. Consensus-based evidence on the use of MRI-VI-RADS for bladder cancer care is needed to serve as a benchmark for formulating guidelines and research agendas until further evidence from randomized trials becomes available.
BACKGROUND: Fertility centre websites are a key sources of information on medically assisted reproduction (MAR) for both infertile people and the general public. As part of a global fertility market, they are also a window to attract potential future patients. They give formal and practical information but in the way the information is displayed, they also convey social representations, and in particular, gender representation in its intersectional dimension. The objective is to analyse the sex, class and race representations regarding reproduction and parenthood that are embedded in the content of fertility centre websites in eight European countries. METHODS: The 5 most visible fertility centres that appeared in the first places on Internet search were selected for each country under study, except for one country which has only three fertility centres. In total, 38 fertility centre websites were considered for a thematic analysis using an iterative approach and a comprehensive perspective. RESULTS: Each centre details its services and techniques according to the legal provisions in force in its country. However, on all the websites studied, the fertility centres demonstrate a strong gendered representation. The logos generally depict women or parts of their bodies, as do the photos, which mainly show white women with light eyes. The description of the causes of infertility and the techniques offered by the centres also highlights gender differences. Sperm donation, where MAR is reserved for heterosexual couples, is included among the techniques for women with the comment that it will enable them to fulfil their dream of becoming mothers. CONCLUSIONS: MAR, and through it the project of having a child and procreative work, is presented as a matter for white, cisgender and heterosexual women, thus fueling stratified reproduction and limiting reproductive justice. The research team formulated guidelines for fertility centres to encourage them to adopt a more inclusive approach in terms of sex, social class and race, so that the diversity of infertile people feel involved and welcome in these centres, to avoid misperceptions about infertility in the general population and to reinforce autonomy and justice in reproductive matters.
- MeSH
- asistovaná reprodukce * MeSH
- infertilita psychologie MeSH
- internet MeSH
- kliniky reprodukční medicíny MeSH
- lidé MeSH
- rozmnožování MeSH
- socioekonomické faktory MeSH
- společenská třída MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Evropa MeSH
The effective treatment of inflammatory diseases, particularly their chronic forms, is a key task of modern medicine. Herein, we report the synthesis and evaluation of biocompatible polymer conjugates based on N-2-(hydroxypropyl)methacrylamide copolymers enabling the controlled release of acetylsalicylic acid (ASA)-based anti-inflammatory drugs under specific stimuli. All polymer nanotherapeutics were proposed as water-soluble drug delivery systems with a hydrodynamic size below 10 nm ensuring suitability for the parenteral application and preventing opsonization by the reticuloendothelial system. The nanotherapeutics bearing an ester-bound ASA exhibited long-term release of the ASA/salicylic acid mixture, while the nanotherapeutics carrying salicylic acid hydrazide (SAH) ensured the selective release of SAH in the acidic inflammatory environment thanks to the pH-sensitive hydrazone bond between the polymer carrier and SAH. The ASA- and SAH-containing nanotherapeutics inhibited both cyclooxygenase isoforms and/or the production of pro-inflammatory mediators. Thanks to their favorable design, they can preferentially accumulate in the inflamed tissue, resulting in reduced side effects and lower dosage, and thus more effective and safer treatment.
- MeSH
- akrylamidy chemie farmakologie aplikace a dávkování MeSH
- antiflogistika farmakologie aplikace a dávkování chemie MeSH
- Aspirin * aplikace a dávkování farmakologie chemie MeSH
- cyklooxygenasy metabolismus MeSH
- inhibitory cyklooxygenasy farmakologie aplikace a dávkování chemie MeSH
- léky s prodlouženým účinkem * MeSH
- mediátory zánětu metabolismus MeSH
- myši MeSH
- nanočástice * chemie MeSH
- nosiče léků chemie MeSH
- polymery * chemie aplikace a dávkování MeSH
- uvolňování léčiv MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Osteosarcoma and Ewing sarcoma are bone tumors mostly diagnosed in children, adolescents, and young adults. Despite multimodal therapy, morbidity is high and survival rates remain low, especially in the metastatic disease setting. Trials investigating targeted therapies and immunotherapies have not been groundbreaking. Better understanding of biological subgroups, the role of the tumor immune microenvironment, factors that promote metastasis, and clinical biomarkers of prognosis and drug response are required to make progress. A prerequisite to achieve desired success is a thorough, systematic, and clinically linked biological analysis of patient samples, but disease rarity and tissue processing challenges such as logistics and infrastructure have contributed to a lack of relevant samples for clinical care and research. There is a need for a Europe-wide framework to be implemented for the adequate and minimal sampling, processing, storage, and analysis of patient samples. Two international panels of scientists, clinicians, and patient and parent advocates have formed the Fight Osteosarcoma Through European Research consortium and the Euro Ewing Consortium. The consortia shared their expertise and institutional practices to formulate new guidelines. We report new reference standards for adequate and minimally required sampling (time points, diagnostic samples, and liquid biopsy tubes), handling, and biobanking to enable advanced biological studies in bone sarcoma. We describe standards for analysis and annotation to drive collaboration and data harmonization with practical, legal, and ethical considerations. This position paper provides comprehensive guidelines that should become the new standards of care that will accelerate scientific progress, promote collaboration, and improve outcomes.
- MeSH
- banky biologického materiálu MeSH
- Ewingův sarkom * terapie patologie diagnóza MeSH
- lidé MeSH
- nádorové biomarkery MeSH
- nádory kostí * terapie patologie MeSH
- odběr biologického vzorku * metody normy MeSH
- osteosarkom * terapie patologie diagnóza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Geografické názvy
- Evropa MeSH
There is increasing pharmaceutical interest in deep eutectic solvents not only as a green alternative to organic solvents in drug manufacturing, but also as liquid formulation for drug delivery. The present work introduces a hydrophobic deep eutectic solvent (HDES) to the field of lipid-based formulations (LBF). Phase behavior of a mixture with 2:1 M ratio of decanoic- to dodecanoic acid was studied experimentally and described by thermodynamic modelling. Venetoclax was selected as a hydrophobic model drug and studied by atomistic molecular dynamics simulations of the mixtures. As a result, valuable molecular insights were gained into the interaction networks between the different components. Moreover, experimentally the HDES showed greatly enhanced drug solubilization compared to conventional glyceride-based vehicles, but aqueous dispersion behavior was limited. Hence surfactants were studied for their ability to improve aqueous dispersion and addition of Tween 80 resulted in lowest droplet sizes and high in vitro drug release. In conclusion, the combination of HDES with surfactant(s) provides a novel LBF with high pharmaceutical potential. However, the components must be finely balanced to keep the integrity of the solubilizing HDES, while enabling sufficient dispersion and drug release.
- MeSH
- farmaceutická chemie metody MeSH
- hydrofobní a hydrofilní interakce * MeSH
- kyseliny laurové chemie MeSH
- lipidy * chemie MeSH
- oleje chemie MeSH
- polysorbáty chemie MeSH
- povrchově aktivní látky * chemie MeSH
- příprava léků * metody MeSH
- rozpouštědla * chemie MeSH
- rozpustnost * MeSH
- simulace molekulární dynamiky * MeSH
- sulfonamidy chemie aplikace a dávkování MeSH
- uvolňování léčiv * MeSH
- Publikační typ
- časopisecké články MeSH
A film-forming system (FFS) represents a convenient topical dosage form for drug delivery. In this study, a non-commercial poly(lactic-co-glycolic acid) (PLGA) was chosen to formulate an FFS containing salicylic acid (SA) and methyl salicylate (MS). This unique combination is advantageous from a therapeutic point of view, as it enabled modified salicylate release. It is beneficial from a technological perspective too, because it improved thermal, rheological, and adhesive properties of the in situ film. DSC revealed complete dissolution of SA and good miscibility of MS with the polymer. MS also ensures optimal viscoelastic and adhesive properties of the film, leading to prolonged and sustained drug release. The hydrolysis of MS to active SA was very slow at skin pH 5.5, but it apparently occurred at physiological pH 7.4. The film structure is homogeneous without cracks, unlike some commercial preparations. The dissolution study of salicylates revealed different courses in their release and the influence of MS concentration in the film. The formulated PLGA-based FFS containing 5 % SA and 10 % MS is promising for sustained and prolonged local delivery of salicylates, used mainly for keratolytic and anti-inflammatory actions and pain relief.
- MeSH
- aplikace kožní MeSH
- aplikace lokální MeSH
- farmaceutická chemie metody MeSH
- koncentrace vodíkových iontů MeSH
- kopolymer kyseliny glykolové a mléčné * chemie MeSH
- kůže metabolismus MeSH
- kyselina mléčná * chemie MeSH
- kyselina polyglykolová * chemie MeSH
- kyselina salicylová * aplikace a dávkování chemie farmakokinetika MeSH
- lékové transportní systémy * metody MeSH
- léky s prodlouženým účinkem MeSH
- rozpustnost MeSH
- salicylany * aplikace a dávkování chemie farmakokinetika MeSH
- uvolňování léčiv MeSH
- Publikační typ
- časopisecké články MeSH
Mesalazin nebo také kyselina 5-aminosalicylová (5-ASA) je látka používaná k léčbě idiopatických střevních zánětů (IBD – inflammatory bowel disease), které představují ulcerózní kolitida (UC) a Crohnova choroba (CN). Mesalazin je na trhu přítomen v různých lékových formách od čípků, nálevů, potahovaných tablet, tablet s prodlouženým uvolňováním až po formu granulí s prodlouženým uvolňováním. Odlišnost lékových forem přináší flexibilitu použití 5-ASA v praxi a umožňuje jeho distribuci a působení od tenkého střeva až po distálněji lokalizované záněty v trávicí trubici. Text diskutuje problematiku dopadů různých lékových forem na farmakokinetiku látky a jejich možný dopad na benefit léčby.
Mesalazine or 5-aminosalicylic acid is important substance which is used in therapy of inflammatory bowel disease (IBD), like ulcerative colitis (UC) and Crohn’s disease (CD). On the market, various mesalazine formulations for local (supositoria, rectal foam and enema) and for systemic administration (covered tablets, slow releasing tablets or slow releasing granulates) are available. Some differences between mesalazine formulations are enabling higher flexibility for clinical practice to choose the optimal drug in terms of distribution active drug according to disease activity and location. The pharmacokinetic profile of various mesalazine formulations and impact on the clinical practice are discussed in the text.
- MeSH
- antiflogistika nesteroidní MeSH
- idiopatické střevní záněty farmakoterapie MeSH
- lékové formy * MeSH
- lidé MeSH
- mesalamin * farmakokinetika farmakologie terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH