Proteins, peptides and nucleic acids are commonly isolated and purified in almost all bioscience laboratories. Methods based on molecular recognition are currently the most powerful tool in separation processes due to their selectivity and recovery. The aim of this study was to prove the versatility and the ability of an affinity carrier containing the immobilised ligand oracin (previously developed by our workgroup) to selectively bind carbonyl-reducing enzymes. These enzymes play an important role in metabolic pathways of various endogenic compounds and xenobiotics. Many important drugs, such as doxorubicin, daunorubicin, haloperidol and the model anticancer drug oracin, are metabolised by carbonyl-reducing enzymes. The functionality of the presented carrier was demonstrated with pure recombinant enzymes (AKR1A1, AKR1B1, AKR1B10, AKR1C1, AKR1C2, AKR1C3, AKR1C4, CBR1 and CBR3) as well as with two model biological samples (cell extract from genetically modified Escherichia coli and pre-purified human liver cytosol). Enzymes that show an affinity toward oracin were efficiently captured, gently eluted using 150 mM ammonium hydroxide and subsequently identified by MS. The method is highly selective and robust and may be applied to the purification and identification of various carbonyl-reducing enzymes from any biological sample.

• Klíčová slova
• Affinity chromatography, Carbonyl-reducing enzymes, Chemical proteomics, Magnetic microparticles, Oracin,
• MeSH
• alkoholoxidoreduktasy metabolismus   MeSH
• cytosol metabolismus   MeSH
• Escherichia coli metabolismus   MeSH
• ethanolaminy metabolismus   MeSH
• hydroxid amonný metabolismus   MeSH
• isochinoliny metabolismus   MeSH
• játra metabolismus   MeSH
• léčivé přípravky metabolismus   MeSH
• lidé MeSH
• ligandy MeSH
• nosiče léků metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• alkoholoxidoreduktasy MeSH
• ethanolaminy MeSH
• hydroxid amonný MeSH
• isochinoliny MeSH
• léčivé přípravky MeSH
• ligandy MeSH
• nosiče léků MeSH
• oracine MeSH Prohlížeč

There is increasing research interest in using mesoporous silica for the delivery of poorly water-soluble drugs that are stabilized in a noncrystalline form. Most research has been done on ordered silica, whereas far fewer studies have been published on using nonordered mesoporous silica, and little is known about intrinsic drug affinity to the silica surface. The present mechanistic study uses inverse gas chromatography (IGC) to analyze the surface energies of three different commercially available disordered mesoporous silica grades in the gas phase. Using the more drug-like probe molecule octane instead of nitrogen, the concept of a "drug-accessible surface area" is hereby introduced, and the effect on drug monolayer capacity is addressed. In addition, enthalpic interactions of molecules with the silica surface were calculated based on molecular mechanics, and entropic energy contributions of volatiles were estimated considering molecular flexibility. These free energy contributions were used in a regression model, giving a successful comparison with experimental desorption energies from IGC. It is proposed that a simplified model for drugs based only on the enthalpic interactions can provide an affinity ranking to the silica surface. Following this preformulation research on mesoporous silica, future studies may harness the presented concepts to guide formulation scientists.

• Klíčová slova
• drug-accessible surface area, drug−silica interaction prediction, inverse gas chromatography, mesoporous silica carrier, modeling-based prediction, monolayer capacity,
• MeSH
• léčivé přípravky MeSH
• oxid křemičitý * chemie   MeSH
• poréznost MeSH
• rozpustnost MeSH
• voda * chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• léčivé přípravky MeSH
• oxid křemičitý * MeSH
• voda * MeSH

INTRODUCTION: Enoyl-(acyl-carrier-protein) reductase (ENR) is a limiting step enzyme in the Fatty Acid Synthase II system. In mammals, there is no homologue to ENR, which makes it an optimal candidate target for selective anti-infective drugs. Up-to-date, only two ENR inhibitors are used in clinical practice. AREA COVERED: This review is a survey on important patents on low molecular weight compounds with ENR inhibiting activity published in 2011-2015. Common patent databases (SciFinder, esp@cenet, WIPO) were used to locate patent applications on the proposed topic and in the timespan of 2011-2015. EXPERT OPINION: In 2011-2015, we have observed patents in previously known structural groups of diphenyl ethers and acrylamides as well as new structural classes, often identified by high-throughput screening campaigns. The spectrum of activity of applied derivatives covers significant bacteria, mycobacteria, and apicomplexan parasites (Plasmodia and Toxoplasma). Good news from research of ENR inhibitors: a) four selective anti-staphylococcal compounds applied in 2011-2015 or earlier were pushed to Phase I or Phase II clinical trials and some of them proved safety and tolerability after peroral and/or intravenous administration; b) big pharma companies have renewed their interest in the development of new anti-infective compounds against resistant strains of clinical relevance.

• Klíčová slova
• Acrylamide, FabI, InhA, MRSA, antibacterial, antimycobacterial, enoyl-acyl-carrier-protein reductase, triclosan,
• MeSH
• antibiotická rezistence MeSH
• antiinfekční látky škodlivé účinky   farmakologie   terapeutické užití   MeSH
• enoyl-ACP-reduktasa (NADH) antagonisté a inhibitory   metabolismus   MeSH
• inhibitory enzymů škodlivé účinky   farmakologie   terapeutické užití   MeSH
• lidé MeSH
• patenty jako téma MeSH
• racionální návrh léčiv MeSH
• rychlé screeningové testy MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antiinfekční látky MeSH
• enoyl-ACP-reduktasa (NADH) MeSH
• inhibitory enzymů MeSH

The carbosilane metallodendrimer G1-[[NCPh(o-N)Ru(η6- p-cymene)Cl]Cl]4 (CRD13), based on an arene Ru(II) complex coordinated to imino-pyridine surface groups, has been conjugated with anti-cancer drugs. Ruthenium in the positively-charged dendrimer structure allows this nanoparticle to be considered as an anticancer drug carrier, made more efficient because ruthenium has anticancer properties. The ability of CRD13 to form complexes with Doxorubicin (DOX), 5-Fluorouracil (5-Fu), and Methotrexate (MTX) has been evaluated using zeta potential measurement, transmission electron microscopy (TEM) and computer simulation. The results show that it forms stable nanocomplexes with all those drugs, enhancing their effectiveness against MDA-MB-231 cancer cells. In vivo tests indicate that the CRD13/DOX system caused a decrease of tumor weight in mice with triple negative breast cancer. However, the tumors were most visibly reduced when naked dendrimers were injected.

• Klíčová slova
• Anticancer drug, Cytotoxicity, Dendrimer, Drug delivery, In vitro, In vivo, Molecular dynamics, Molecular simulations, Ruthenium, Tumor weight,
• MeSH
• komplexní sloučeniny * chemie   MeSH
• lidé MeSH
• molekulární struktura MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nosiče léků MeSH
• počítačová simulace MeSH
• protinádorové látky * chemie   MeSH
• ruthenium * chemie   MeSH
• screeningové testy protinádorových léčiv MeSH
• triple-negativní karcinom prsu * farmakoterapie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• carbosilane MeSH Prohlížeč
• komplexní sloučeniny * MeSH
• nosiče léků MeSH
• protinádorové látky * MeSH
• ruthenium * MeSH

Nanodiamonds represent an attractive potential carrier for anticancer drugs. The main advantages of nanodiamond particles with respect to medical applications are their high compatibility with non-cancerous cells, feasible surface decoration with therapeutic and cancer-cell targeting molecules, and their relatively low manufacturing cost. Additionally, nanodiamond carriers significantly increase treatment efficacy of the loaded drug, so anticancer drugs execute more effectively at a lower dose. Subsequently, lower drug dose results in less extensive side effects. The carriers decorated with a targeting molecule accumulate primarily in the tumor tissue, and those nanodiamond particles impair efflux of the drug from cancer cells. Therapeutic approaches considering nanodiamond carriers were already tested in vitro, as well as in vivo. Now, researchers focus particularly on the possible side effects of nanodiamond carriers applied systemically in vivo. The behavior of nanodiamond carriers depends heavily on their surface coatings, so each therapeutic complex must be evaluated separately. Generally, it seems that site-specific application of nanodiamond carriers is a rather safe therapeutic approach, but intravenous application needs further study. The benefits of nanodiamond carriers are remarkable and represent a potent approach to overcome the drug resistance of many cancers.

• Klíčová slova
• Nanodiamond, cancer therapy, drug carrier, drug resistance, nanoparticles,
• Publikační typ
• časopisecké články MeSH
• přehledy 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.

• Klíčová slova
• PLA/PEG fibers, cytotoxicity, drug release, local chemotherapy, paclitaxel,
• 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
• protinádorové látky * chemie   farmakokinetika   farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• léky s prodlouženým účinkem MeSH
• nosiče léků * MeSH
• paclitaxel * MeSH
• poly(lactide) MeSH Prohlížeč
• polyestery * MeSH
• polyethylenglykoly * MeSH
• protinádorové látky * MeSH

The enzymatic release of a model drug from a polymer carrier inside a tumor using multispectral optical imaging in vivo in nude mice bearing colorectal carcinomas HT-29 and DLD-1 is demonstrated. Much higher release rate in vivo from a linear (30 kDa) (N-2-hydroxypropyl)methacrylamide-based polymer compared with a high molecular weight branched (170 kDa) polymer conjugate is observed, probably due to steric hindrance of the cleavable spacer of the latter polymer to proteolytic enzymes. There is no significant difference in the relative biodistribution of the two polymers, but the branched polymer circulates much longer. Both polymers are labeled with two different fluorophores. Dyomics-676 as a drug model is attached to the polymer via an enzymatically cleavable Gly-Phe-Leu-Gly spacer; Dyomics 782 is bound to the same polymer via a nondegradable amide bond, enabling the tracking of the polymer carrier after i.v. application to mice.

• Klíčová slova
• EPR effect, enzymatic release, in vivo imaging, polymer drug carriers, tumor targeting,
• MeSH
• akrylamidy * chemie   farmakokinetika   farmakologie   MeSH
• fluorescenční barviva * chemie   farmakokinetika   farmakologie   MeSH
• kolorektální nádory * farmakoterapie   metabolismus   patologie   MeSH
• lidé MeSH
• myši nahé MeSH
• myši MeSH
• nosiče léků * chemie   farmakokinetika   farmakologie   MeSH
• xenogenní modely - testy protinádorové aktivity MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• akrylamidy * MeSH
• fluorescenční barviva * MeSH
• N-(2-hydroxypropyl)methacrylamide MeSH Prohlížeč
• nosiče léků * MeSH

Lignin nanoparticles synthesis is among recent developments in lignin valorization especially for biomedical applications. In this study, a new technique where complete self-assembling of lignin was ensured by simultaneous solvent displacement and flash pH change was used to optimize particle size of blank lignin nanoparticles (BLNPs) for suitability in cell uptake along with maximized yield. To establish BLNPs as drug carrier, safety studies including hemocompatibility, cytotoxicity and elaborate genotoxicity studies on Drosophila melanogaster as a model organism were done. Finally, irinotecan loaded lignin nanoparticles (DLNPs) were synthesized to establish their drug carrying potential and thorough in vitro characterization was performed. BLNPs with controllable size (⁓152 nm), low polydispersity (<0.2), maximized yield (>65%), negative surface charge (-22 to -23 mV), spherical shape and smooth surface were obtained with acceptable %hemolysis (<2%). In vitro cytotoxicity studies revealed that BLNPs were significantly toxic (74.38 ± 4.74%) in human breast adenocarcinoma (MCF-7), slightly toxic (38.8 ± 4.70%) in human alveolar epithelial adenocarcinoma (A-549) and insignificantly toxic (15.89 ± 2.84%) to human embryonic kidney (HEK-293) cells. BLNPs showed concentration dependent early neuronal defects in Drosophila, but nuclei fragmentation and gut cell damage were absent. Sustained release DLNPs with high drug loading reduced the IC50 value of irinotecan by almost 3 folds.

• Klíčová slova
• Cytocompatibility, Genotoxicity, Lignin, QbD based optimization, Sustained release,
• MeSH
• buněčné linie MeSH
• buňky A549 MeSH
• Drosophila melanogaster účinky léků   MeSH
• HEK293 buňky MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• lignin škodlivé účinky   chemie   MeSH
• MFC-7 buňky MeSH
• nádorové buněčné linie MeSH
• nanočástice škodlivé účinky   chemie   MeSH
• nosiče léků škodlivé účinky   chemie   MeSH
• potkani Wistar MeSH
• velikost částic MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• lignin MeSH
• nosiče léků MeSH

Halloysite is a naturally occurring mineral similar to kaolin, possessing a special particle shape in the form of ultramicroscopic multi-layered hollow cylinders. It is utilizable in many industrial branches and due to its advantages, e.g. biocompatibility, drug entrapment, high mechanical strength and easy natural availability also on the pharmaceutical field and in medicine. It can bind drugs on the surface or inside of tubules and increase drug stability or change its release. Surface of the tubules can be readily modified for the application in drug delivery systems. Halloysite was reported as promising material for bone implants and controlled delivery of biomacromolecules. This review is dealing with pharmaceutical and biomedical usage of this interesting material and is including original experimental work published recently.

• MeSH
• jíl MeSH
• lékové transportní systémy * MeSH
• nanotrubičky * MeSH
• nosiče léků * MeSH
• silikáty hliníku * MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• jíl MeSH
• nosiče léků * MeSH
• silikáty hliníku * MeSH

Salmonella carrier state (42.6%-S. enteritidis and 34.4%-S. dublin) was demonstrated in subjects after acute salmonellosis as well as in healthy persons infected with salmonella as a result of occupational exposure to poultry (8.8% in humans exposed to chickens and 6.1% in those exposed to ducks) and sheep (2.8%). The carrier state was accompanied by intermittent pain in the epigastrium, diminished appetite, diarrhoea etc. Most of the carrier subjects with a history of salmonellosis exhibited, upon rectoromanoscopy, a varying degree of proctosigmoiditsi. The etiological role of S. typhimurium was proved beyond doubt, as well as its ability to cause salmonellosis outbursts, sporadic cases of the disease and the carrier state. When large industrial facilities specializing in poultry processing were investigated, the salmonella carrier state was revealed in practically healthy poultry--in 16% of chickens and 12% of ducks. The salmonella organisms isolated from carrier persons had, with some exceptions, typical properties, being virulent in that they caused death of experimental animals, seeded their internal organs and induced pathogenicity-associated enzymes. Multiple resistance to antibiotics was demonstrated in salmonella isolated from poultry; also determined was its plasmid nature. Pronounced resistance of the above salmonella subtypes to tetracycline-related antibiotics and streptomycin may be due to the fact that these drugs are used in poultry raising.

• MeSH
• drůbež MeSH
• lidé MeSH
• nemoci drůbeže mikrobiologie   přenos   MeSH
• nemoci zemědělců mikrobiologie   přenos   MeSH
• přenašečství * MeSH
• Salmonella enteritidis izolace a purifikace   MeSH
• Salmonella izolace a purifikace   MeSH
• salmonelová infekce u zvířat mikrobiologie   přenos   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH