Free radical polymerization technique was used to formulate Poloxamer-188 based hydrogels for controlled delivery. A total of seven formulations were formulated with varying concentrations of polymer, monomer ad cross linker. In order to assess the structural properties of the formulated hydrogels, Fourier Transform Infrared Spectroscopy (FTIR), Thermogravimetric analysis (TGA), Differential Scanning Calorimetry (DSC), Scanning electron microscopy (SEM), and X-ray diffraction (XRD) were carried out. To assess the effect of pH on the release of the drug from the polymeric system, drug release studies were carried in pH 1.2 and 7.4 and it was found that release of the drug was significant in pH 7.4 as compared to that of pH 1.2 which confirmed the pH responsiveness of the system. Different kinetic models were also applied to the drug release to evaluate the mechanism of the drug release from the system. To determine the safety and biocompatibility of the system, toxicity study was also carried out for which healthy rabbits were selected and formulated hydrogels were orally administered to the rabbits. The results obtained suggested that the formulated poloxamer-188 hydrogels are biocompatible with biological system and have the potential to serve as controlled drug delivery vehicles.

• MeSH
• akrylové pryskyřice * chemie   MeSH
• diferenciální skenovací kalorimetrie MeSH
• difrakce rentgenového záření MeSH
• hydrogely * chemie   MeSH
• koncentrace vodíkových iontů MeSH
• králíci MeSH
• lékové transportní systémy MeSH
• léky s prodlouženým účinkem chemie   farmakokinetika   MeSH
• mikroskopie elektronová rastrovací MeSH
• nosiče léků chemie   MeSH
• poloxamer * chemie   MeSH
• spektroskopie infračervená s Fourierovou transformací MeSH
• termogravimetrie MeSH
• timolol * aplikace a dávkování   farmakokinetika   chemie   MeSH
• uvolňování léčiv MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

A family of new compounds with sulfonamide and amide functional groups as potential Alzheimer's disease drugs were prepared by multistep synthesis. Thermal stability measurements recorded the initial decomposition in the range of 200-220°C, close above the melting point. The final compounds were tested for their ability to inhibit acetylcholinesterase and butyrylcholinesterase, and the in vitro dissolution behavior of selected compounds was studied through both lipophilic and hydrophilic matrix tablets. All nine tested derivatives were even more active in inhibiting acetylcholinesterase than the clinically used rivastigmine. Regression analysis of the obtained dissolution profiles was performed, and the effects of the pH and the release mechanism were determined. Some substances showed remarkable biological activity and became a subject of interest for further extensive study.

• MeSH
• acetylcholinesterasa metabolismus   MeSH
• Alzheimerova nemoc * farmakoterapie   MeSH
• butyrylcholinesterasa * metabolismus   MeSH
• cholinesterasové inhibitory * farmakologie   chemická syntéza   chemie   MeSH
• koncentrace vodíkových iontů MeSH
• lidé MeSH
• molekulární struktura MeSH
• rivastigmin farmakologie   chemická syntéza   chemie   MeSH
• rozpustnost MeSH
• sulfonamidy * farmakologie   chemie   chemická syntéza   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Úvod: Velké intrakoronární tromby u pacientů s infarktem myokardu s elevacemi úseku ST (STEMI) mohou způsobit distální embolizaci, fenomén „no-reflow“ a trombózu stentu. Přibližně u 10 % pacientů podstupujících primární perkutánní koronární intervenci (PCI) dochází k distální embolizaci trombu, což způsobuje mikrovaskulární obstrukci koronárních tepen a snížení perfuze myokardiální tkáně. To může mít za následek přetrvávající ischemii, větší velikost infarktu a významné zvýšení 30denní mortality, a to bez ohledu na úspěšnou PCI s normálním průtokem epikardiálními cévami. Kazuistika: Jedenapadesátiletý muž asijského původu byl přijat s diagnózou STEMI. Koronarografie prokázala velký trombus obturující proximální část levé koronární tepny (ACS). Poté, co opakované pokusy o manuální aspirační trombektomii (MAT) a balonkovou angioplastiku nevedly k obnovení průtoku krve koronárními tepnami, byla provedena katetrizační intrakoronární trombolýza s aplikací streptokinázy. Po úspěšném zavedení stentu zůstal v ACS difuzní reziduální trombus. Angiografické zhodnocení ACS provedené o čtyři dny později prokázalo úplné rozpuštění trombu s průtokem infarktovou tepnou TIMI 3. Diskuze: I když v oblasti léčby intrakoronárního trombu neexistuje zlatý standard, je možné využít kombinace farmakologické a mechanické léčby. MAT by v případě STEMI neměla být používána rutinně, nicméně ve vybraných případech může být užitečná. Katetrizační intrakoronární trombolýza může být bezpečnou a účinnou alternativou reperfuzní strategie, pokud MAT samotnou nedosáhneme dostatečného průtoku krve infarktovou tepnou (IRA). Závěr: Řešení intrakoronárního trombu během PCI je i nadále terapeutickou výzvou, přičemž lepších výsledků lze dosáhnout pomocí agresivního, individuálního přístupu šitého na míru.

Introduction: Large intracoronary thrombus in patients presenting with ST elevation myocardial infarction (STEMI) can cause distal embolization, the no-reflow phenomenon, and stent thrombosis. Approximately 10% of patients undergoing primary percutaneous coronary intervention (PCI) have distal embolization of thrombus, causing coronary microvascular obstruction and reduced myocardial tissue perfusion. This can lead to ongoing ischemia, a larger infarct size, and a significant increase in 30-day mortality, regardless of successful PCI with normal epicardial vessel flow. Case Presentation: A 51-year-old Asian male presented with STEMI. Coronary angiography revealed a large thrombus totally occluding the proximal portion of the right coronary artery (RCA). Catheter-directed intracoronary thrombolysis with streptokinase was performed after multiple attempts at manual aspiration thrombectomy (MAT) and balloon angioplasty had failed to achieve coronary blood flow recovery. After successful stenting, a diffuse residual thrombus remained in the RCA. Evaluation angiography of the RCA performed four days later showed complete thrombus dissolution with thrombolysis in myocardial infarction (TIMI) grade 3 flow. Discussion: While there is no gold-standard therapy to deal with intracoronary thrombus, there are combinations of both pharmacological and mechanical therapies that can be utilized. MAT should not be used routinely in STEMI, but may be helpful in selected cases. Catheter-directed intracoronary thrombolysis can be a safe and effective alternative reperfusion strategy when MAT alone fails to achieve sufficient coronary blood flow in the thrombotic infarct-related artery (IRA). Conclusion: The management of intracoronary thrombus during PCI remains a therapeutic challenge, and an aggressive, case-by-case, tailored approach can lead to improved outcomes.

• MeSH
• antikoagulancia terapeutické užití   MeSH
• Asijci MeSH
• fibrinolytika terapeutické užití   MeSH
• infarkt myokardu s elevacemi ST úseků chirurgie   MeSH
• inhibitory agregace trombocytů terapeutické užití   MeSH
• koronární angiografie MeSH
• koronární trombóza * chirurgie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mechanická trombolýza * metody   MeSH
• nemoci koronárních tepen chirurgie   MeSH
• streptokinasa terapeutické užití   MeSH
• trombolytická terapie metody   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

Cévní mozková příhoda, infarkt myokardu a plicní embolie představují významnou zdravotní zátěž pro současnou společnost, přičemž jejich hlavní příčinou jsou krevní sraženiny a poškození vnitřní výstelky cév (endotelu). Přesná a rychlá diagnostika těchto sraženin, zejména určení jejich stáří, je klíčová pro optimální volbu léčebného postupu, jako je trombolýza (farmakologické rozpuštění sraženiny) nebo trombektomie (mechanické odstranění sraženiny). Stávající diagnostické metody však nedosahují požadované úrovně přesnosti a efektivity. Tento článek zkoumá potenciál jodovaných nanočástic (IoNP) na bázi polyjodovaných biodegradabilních polymerů, které mohou cíleně vyhledávat specifické složky, jako je fibrin, a umožnit tak vizualizaci krevních sraženin pomocí rentgenových zobrazovacích metod, jako je počítačová tomografie (CT) nebo skiaskopie. Nanočástice mají schopnost nejen zobrazit sraženiny, ale také odhadnout jejich stáří, což by mohlo výrazně podpořit moderní teranostický přístup, který kombinuje diagnostiku a terapii. Článek také demonstruje možnosti testování farmakokinetiky těchto teranostik pomocí modelového organismu (potkana), využívající metodu laserové ablace s hmotnostní spektrometrií s indukčně vázaným plazmatem. Tento přístup přispívá k lepšímu porozumění biodegradability potenciálních léčiv a představuje klíčový krok v preklinickém hodnocení.

Stroke, myocardial infarction, and pulmonary embolism represent a significant health burden for modern society, with their primary causes being blood clots and damage to the endothelial lining of blood vessels. Accurate and rapid diagnosis of these clots, particularly determining their age, is crucial for optimal treatment selection, such as thrombolysis (pharmacological dissolution of the clot) or thrombectomy (mechanical removal of the clot). However, existing diagnostic methods do not achieve the required levels of accuracy and efficiency. This article explores the potential of iodinated nanoparticles (IoNPs) based on polyiodinated biodegradable polymers, which can selectively target specific components such as fibrin, thereby enabling visualization of blood clots using X-ray imaging techniques like computed tomography (CT) or fluoroscopy. The nanoparticles have the capability not only to visualize clots but also to estimate their age, which could significantly support a modern theranostic approach that combines diagnosis and therapy. The article also demonstrates the possibilities of testing the pharmacokinetics of these theranostics using a model organism (rat), employing the method of laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). This approach contributes to a better understanding of the biodegradability of potential therapeutics and represents a key step in preclinical evaluation.

• MeSH
• cévní mozková příhoda diagnostické zobrazování   terapie   MeSH
• diagnostické zobrazování MeSH
• kontrastní látky MeSH
• lidé MeSH
• nanočástice MeSH
• teranostická nanomedicína * metody   MeSH
• trombektomie MeSH
• trombolytická terapie MeSH
• trombóza diagnostické zobrazování   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

Due to the possibility of designing various spatial structures, three-dimensional printing can be implemented in the production of customized medicines. Nevertheless, the use of these methods for the production of dosage forms requires further optimization, understanding, and development of printouts' quality verification mechanisms. Therefore, the goal of our work was the preparation and advanced characterization of 3D printed orodispersible tablets (ODTs) containing fluconazole, printed by the fused deposition modeling (FDM) method. We prepared and analyzed 7 printable filaments containing from 10% to 70% fluconazole, used as model API. Obtaining a FDM-printable filament with such a high API content makes our work unique. In addition, we confirmed the 12-month stability of the formulation, which, to our knowledge, is the first study of this type. Next, we printed 10 series of porous tablets containing 50 mg of API from both fresh and stored filaments containing 20 %, 40 %, or 70 % fluconazole. We confirmed the high quality and precision of the printouts using scanning electron microscopy. The detailed analysis of the tablets' disintegration process included the Pharmacopeial test, but also the surface dissolution imaging analysis (SDI) and the test simulating oral conditions performed in own-constructed apparatus. For each composition, we obtained tablets disintegrating in less than 3 min, i.e., meeting the criteria for ODTs required by the European Pharmacopeia. The filaments' storage at ambient conditions did not affect the quality of the tablets. All printed tablets released over 95% of the fluconazole within 30 min. Moreover, the printouts were stable for two weeks.

• MeSH
• 3D tisk * MeSH
• farmaceutická technologie metody   MeSH
• flukonazol * MeSH
• poréznost MeSH
• tablety chemie   MeSH
• uvolňování léčiv MeSH
• Publikační typ
• časopisecké články MeSH

Introduction: Tissue conditioners have been widely used in various clinical applications in dentistry, such as treating inflamed alveolar ridges, temporarily relining partial and complete dentures, and the acquisition of functional impressions for denture fabrication. This study aimed to investigate the mechanical properties of the most prevalent tissue conditioner materials on the market, including Tissue Conditioners (TC), Visco Gel (VG), and FITT (F). Materials and Methods: The three tissue conditioners, TC, VG, and F, were assessed based on the parameters mentioned above. The following tests were performed based on the ISO 10139-1 and ISO 10139-2 requirements: Shore A hardness, denture plate adhesion, sorption, water solubility, and contraction after 1 and 3 days in water. Additional tests are described in the literature, such as ethanol content and gelling time. The tests were carried out by storing the materials in water at 37 °C for 7 days. Results: The gel times of all tested materials exceeded 5 min (TC = 300 [s], VG = 350 [s]). In vitro, phthalate-free materials exhibited higher dissolution in water after 14 days (VG = -260.78 ± 11.31 μg/mm2) compared to F (-76.12 ± 7.11 μg/mm2) and experienced faster hardening when stored in distilled water (F = 33.4 ± 0.30 Sh. A, VG = 59.2 ± 0.60 Sh. A). They also showed greater contractions. The connection of all materials to the prosthesis plate was consistent at 0.11 MPa. The highest counterbalance after 3 days was observed in TC = 3.53 ± 1.12%. Conclusions: Materials containing plasticizers that are not phthalates have worse mechanical properties than products containing these substances. Since phthalates are not allowed to be used indefinitely in medical devices, additional research is necessary, especially in vivo, to develop safe materials with superior functional properties to newer-generation alternatives. In vitro results often do not agree fully with those of in vivo outcomes.

• MeSH
• kostní destičky * MeSH
• lidé MeSH
• methylmetakryláty * MeSH
• voda MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Long-acting injectable formulations represent a rapidly emerging category of drug delivery systems that offer several advantages compared to orally administered medicines. Rather than having to frequently swallow tablets, the medication is administered to the patient by intramuscular or subcutaneous injection of a nanoparticle suspension that forms a local depot from which the drug is steadily released over a period of several weeks or months. The benefits of this approach include improved medication compliance, reduced fluctuations of drug plasma level, or the suppression of gastrointestinal tract irritation. The mechanism of drug release from injectable depot systems is complex, and there is a lack of models that would enable quantitative parametrisation of the process. In this work, an experimental and computational study of drug release from a long-acting injectable depot system is reported. A population balance model of prodrug dissolution from asuspension with specific particle size distribution has been coupled with the kinetics of prodrug hydrolysis to its parent drug and validated using in vitro experimental data obtained from an accelerated reactive dissolution test. Using the developed model, it is possible to predict the sensitivity of drug release profiles to the initial concentration and particle size distribution of the prodrug suspension, and subsequently simulate various drug dosing scenarios. Parametric analysis of the system has identified the boundaries of reaction- and dissolution-limited drug release regimes, and the conditions for the existence of a quasi-steady state. This knowledge is crucial for the rational design of drug formulations in terms of particle size distribution, concentration and intended duration of drug release.

• MeSH
• antipsychotika * MeSH
• injekce intramuskulární MeSH
• léky s prodlouženým účinkem MeSH
• lidé MeSH
• prekurzory léčiv * MeSH
• rozpustnost MeSH
• suspenze MeSH
• uvolňování léčiv MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Manganese oxides are considered an essential component of natural geochemical barriers due to their redox and sorptive reactivity towards essential and potentially toxic trace elements. Despite the perception that they are in a relatively stable phase, microorganisms can actively alter the prevailing conditions in their microenvironment and initiate the dissolution of minerals, a process that is governed by various direct (enzymatic) or indirect mechanisms. Microorganisms are also capable of precipitating the bioavailable manganese ions via redox transformations into biogenic minerals, including manganese oxides (e.g., low-crystalline birnessite) or oxalates. Microbially mediated transformation influences the (bio)geochemistry of manganese and also the environmental chemistry of elements intimately associated with its oxides. Therefore, the biodeterioration of manganese-bearing phases and the subsequent biologically induced precipitation of new biogenic minerals may inevitably and severely impact the environment. This review highlights and discusses the role of microbially induced or catalyzed processes that affect the transformation of manganese oxides in the environment as relevant to the function of geochemical barriers.

• MeSH
• mangan * chemie   MeSH
• minerály chemie   MeSH
• oxidace-redukce MeSH
• oxidy * chemie   MeSH
• sloučeniny manganu chemie   MeSH
• životní prostředí MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The complexity of drug delivery mechanisms calls for the development of new transport system designs. Here, we report a robust synthetic procedure toward stable glycodendrimer (glyco-DDM) series bearing glucose, galactose, and oligo(ethylene glycol)-modified galactose peripheral units. In vitro cytotoxicity assays showed exceptional biocompatibility of the glyco-DDMs. To demonstrate applicability in drug delivery, the anticancer agent doxorubicin (DOX) was encapsulated in the glyco-DDM structure. The anticancer activity of the resulting glyco-DDM/DOX complexes was evaluated on the noncancerous (BJ) and cancerous (MCF-7 and A2780) cell lines, revealing their promising generation- and concentration-dependent effect. The glyco-DDM/DOX complexes show gradual and pH-dependent DOX release profiles. Fluorescence spectra elucidated the encapsulation process. Confocal fluorescence microscopy demonstrated preferential cancer cell internalization of the glyco-DDM/DOX complexes. The conclusions were supported by computer modeling. Overall, our results are consistent with the assumption that novel glyco-DDMs and their drug complexes are very promising in drug delivery and related applications.

• MeSH
• doxorubicin chemie   farmakologie   MeSH
• lékové transportní systémy metody   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nádory vaječníků * MeSH
• nosiče léků chemie   MeSH
• polyethylenglykoly chemie   MeSH
• protinádorové látky * farmakologie   MeSH
• silany MeSH
• uvolňování léčiv MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The aim of this study was to improve rivaroxaban water-solubility by cocrystal preparation and to understand this process. The screening with water-soluble coformers was performed via both mechanochemical and solution-mediated techniques. Two cocrystals of rivaroxaban with malonic acid and oxalic acid were prepared, and the structure of the cocrystal with oxalic acid was solved. Both cocrystals exhibit improved dissolution properties. The mechanism of the supersaturation maintenance was studied by in-situ Raman spectroscopy. The transformation into rivaroxaban dihydrate was identified as the critical step in the improved dissolution properties of both cocrystals. Moreover, the transformation kinetics and solubilization effects of the coformers were identified as responsible for the differences in the dissolution behavior of the cocrystals. In-vivo experiments proved that the use of cocrystal instead of form I of free API helped to increase the bioavailability ofrivaroxaban.

• MeSH
• difrakce rentgenového záření MeSH
• krystalizace MeSH
• kyselina oxalová MeSH
• rivaroxaban * MeSH
• rozpustnost MeSH
• voda * chemie   MeSH
• Publikační typ
• časopisecké články MeSH