OBJECTIVE: This research aims to design and evaluate an enteric-coated hard capsule dosage form for targeted delivery of biological materials, such as FMT (fecal microbiota transplant) or live microbes, to the distal parts of the GIT. The capsules are designed to be internally protected against destruction by hydrophilic filling during passage through the digestive tract. METHODS: Hard gelatin capsules and DRcapsTMcapsules based on HPMC and gellan were used to encapsulate a hydrophilic body temperature-liquefying gelatin hydrogel with caffeine or insoluble iron oxide mixture. Different combinations of polymers were tested for the internal (ethylcellulose, Eudragit® E, and polyvinyl acetate) and external (Eudragit® S, Acryl-EZE®, and cellacefate) coating. The external protects against the acidic gastric environment, while the internal protects against the liquid hydrophilic filling during passage. Coated capsules were evaluated using standard disintegration and modified dissolution methods for delayed-release dosage forms. RESULTS: Combining suitable internal (ethylcellulose 1.0 %) and external (Eudragit® S 20.0 %) coating of DRcapsTM capsules with the wiping and immersion method achieved colonic release times. While most coated capsules met the pharmaceutical requirements for delayed release, one combination stood out. Colonic times were indicated by the dissolution of soluble caffeine (during 120-720 min) measured by the dissolution method, and capsule rupture was indicated by the release of insoluble iron oxide (after 480 min) measured by the disintegration method. This promising result demonstrates the composition's suitability and potential to protect the content until it's released, inspiring hope for the future of colon-targeted delivery systems and its potential for the pharmaceutical and biomedical fields. CONCLUSION: Innovative and easy capsule coatings offer significant potential for targeted drugs, especially FMT water suspension, to the GIT, preferably the colon. The administration method is robust and not considerably affected by the quantity of internal or external coatings. It can be performed in regular laboratories without specialized individual and personalized treatment equipment, making it a practical and feasible method for drug delivery.

• Klíčová slova
• Capsules, Coating, Immersion method, Novel approach in delayed-release dosage form with potential benefits for individual treatment, Principal component analysis,
• MeSH
• bakteriální polysacharidy chemie   MeSH
• biokompatibilní materiály chemie   MeSH
• celulosa * chemie   analogy a deriváty   MeSH
• deriváty hypromelózy chemie   MeSH
• hydrofobní a hydrofilní interakce * MeSH
• hydrogely chemie   MeSH
• kofein chemie   aplikace a dávkování   MeSH
• kolon * metabolismus   MeSH
• kyseliny polymethakrylové chemie   MeSH
• lékové transportní systémy * metody   MeSH
• léky s prodlouženým účinkem chemie   MeSH
• polymery chemie   MeSH
• polyvinyly chemie   MeSH
• tobolky * MeSH
• uvolňování léčiv * MeSH
• želatina * chemie   MeSH
• železité sloučeniny chemie   aplikace a dávkování   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• bakteriální polysacharidy MeSH
• biokompatibilní materiály MeSH
• celulosa * MeSH
• deriváty hypromelózy MeSH
• ethyl cellulose MeSH Prohlížeč
• ferric oxide MeSH Prohlížeč
• gellan gum MeSH Prohlížeč
• hydrogely MeSH
• kofein MeSH
• kyseliny polymethakrylové MeSH
• léky s prodlouženým účinkem MeSH
• methylmethacrylate-methacrylic acid copolymer MeSH Prohlížeč
• polymery MeSH
• polyvinyl acetate MeSH Prohlížeč
• polyvinyly MeSH
• tobolky * MeSH
• želatina * MeSH
• železité sloučeniny MeSH

The visualization of organs and tissues using 31P magnetic resonance (MR) imaging represents an immense challenge. This is largely due to the lack of sensitive biocompatible probes required to deliver a high-intensity MR signal that can be distinguished from the natural biological background. Synthetic water-soluble phosphorus-containing polymers appear to be suitable materials for this purpose due to their adjustable chain architecture, low toxicity, and favorable pharmacokinetics. In this work, we carried out a controlled synthesis, and compared the MR properties, of several probes consisting of highly hydrophilic phosphopolymers differing in composition, structure, and molecular weight. Based on our phantom experiments, all probes with a molecular weight of ~3-400 kg·mol-1, including linear polymers based on poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC), poly(ethyl ethylenephosphate) (PEEP), and poly[bis(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)]phosphazene (PMEEEP) as well as star-shaped copolymers composed of PMPC arms grafted onto poly(amidoamine) dendrimer (PAMAM-g-PMPC) or cyclotriphosphazene-derived cores (CTP-g-PMPC), were readily detected using a 4.7 T MR scanner. The highest signal-to-noise ratio was achieved by the linear polymers PMPC (210) and PMEEEP (62) followed by the star polymers CTP-g-PMPC (56) and PAMAM-g-PMPC (44). The 31P T1 and T2 relaxation times for these phosphopolymers were also favorable, ranging between 1078 and 2368 and 30 and 171 ms, respectively. We contend that select phosphopolymers are suitable for use as sensitive 31P MR probes for biomedical applications.

• Klíčová slova
• 31P magnetic resonance imaging, controlled polymerization, phosphorus-containing polymers, polymer probes,
• MeSH
• biokompatibilní materiály chemie   MeSH
• fosfor * MeSH
• fosforylcholin chemie   MeSH
• kyseliny polymethakrylové chemie   MeSH
• magnetická rezonanční spektroskopie MeSH
• methakryláty chemie   MeSH
• micely MeSH
• polymery * chemie   MeSH
• povrchové vlastnosti MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biokompatibilní materiály MeSH
• fosfor * MeSH
• fosforylcholin MeSH
• kyseliny polymethakrylové MeSH
• methakryláty MeSH
• micely MeSH
• polymery * MeSH

The cytotoxicity of methacrylate-based biopolymers crosslinked by in situ photopolymerization has been attributed mainly to residual methacrylate monomers released due to incomplete polymerization. The residual monomers, primarily triethyleneglycol dimethacrylate or 2-hydroxyethyl methacrylate, may irritate adjacent tissue, or be released into the bloodstream and reach practically all tissues. Increased production of reactive oxygen species, which may be connected to concomitant glutathione depletion, has been the most noticeable effect observed in vitro following the exposure of cells to methacrylates. Radical scavengers such as glutathione or N-acetylcysteine represent the most important cellular strategy against methacrylate-induced toxicity by direct adduct formation, resulting in monomer detoxification. Reactive oxygen species may participate in methacrylate-induced genotoxic or pro-apoptotic effects and cell-cycle arrest via induction of corresponding molecular pathways in cells. A deeper understanding of the biological mechanisms and effects of methacrylates widely used in various bioapplications may enable a better estimation of potential risks and thus, selection of a more appropriate composition of polymer material to eliminate potentially harmful substances such as triethyleneglycol dimethacrylate.

• Klíčová slova
• HEMA, ROS, TEGDMA, cytotoxicity, genotoxicity,
• MeSH
• acetylcystein farmakologie   MeSH
• biokompatibilní materiály chemie   toxicita   MeSH
• glutathion metabolismus   MeSH
• kyseliny polymethakrylové chemie   toxicita   MeSH
• lidé MeSH
• methakryláty chemie   toxicita   MeSH
• polyethylenglykoly chemie   toxicita   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• scavengery volných radikálů farmakologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• acetylcystein MeSH
• biokompatibilní materiály MeSH
• glutathion MeSH
• hydroxyethyl methacrylate MeSH Prohlížeč
• kyseliny polymethakrylové MeSH
• methakryláty MeSH
• polyethylenglykoly MeSH
• reaktivní formy kyslíku MeSH
• scavengery volných radikálů MeSH
• triethylene glycol dimethacrylate MeSH Prohlížeč

Assemblies of carbohydrate polymers are important in a number of applications and improved methods for their fabrication are increasingly sought after. Herein, we report that an aqueous two-phase system of alginate (Alg) and hydroxypropyl cellulose with poly(methacrylic acid) graft chains (HPC-PMA) facilitated the assembly of Alg/HPC-PMA in both phases. Dynamically formed filamentous domains in a flow field were gelled by rapid complexation with cationic polyethyleneimine (PEI). The fabricated HPC-PMA gel filament morphologies can be switched between the bundled and dissociated gel filaments using a co-flow microfluidic device in response to the amount of supplied PEI crosslinker. Excess complexation of PEI contributes to the fabrication of cationic gel filaments; this contribution results in a dissociated structure due to electrostatic repulsion. In contrast, an appropriate amount of PEI resulted in a bundle structure. The proposed spinning method avoids the risk of nozzle clogging, and enables the one-step spinning of multiple gel filaments.

• Klíčová slova
• Alginate, Aqueous two phase system, Gel fiber, Hydroxypropyl cellulose, Polyion complex,
• MeSH
• celulosa chemická syntéza   chemie   MeSH
• ethery chemická syntéza   chemie   MeSH
• gely chemická syntéza   chemie   MeSH
• ionty chemie   MeSH
• kyseliny polymethakrylové chemie   MeSH
• povrchové vlastnosti MeSH
• termodynamika * MeSH
• velikost částic MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• celulosa MeSH
• ethery MeSH
• gely MeSH
• ionty MeSH
• kyseliny polymethakrylové MeSH
• polymethacrylic acid MeSH Prohlížeč

The cytopoxic effect of RL2 lactaptin (the recombinant analog of proteolytic fragment of human kappa-casein) toward tumor cells in vitro and in vivo presents it as a novel promising antitumor drug. The binding of any drug with serum proteins can affect their activity, distribution, rate of excretion and toxicity in the human body. Here, we studied the ability of RL2 to bind to various blood serum proteins. Using magnetic microparticles bearing by RL2 as an affinity matrix, in combination with mass spectrometry and western blot analysis, we found a number of blood serum proteins possessing affinity for RL2. Among them IgA, IgM and IgG subclasses of immunoglobulins, apolipoprotein A1 and various cortactin isoforms were identified. This data suggests that in the bloodstream RL2 lactaptin takes part in complicate protein-protein interactions, which can affect its activity.

• Klíčová slova
• RL2 antitumor agent, human blood serum proteins, identification, magnetic microparticles, mass spectrometry and western blotting, purification,
• MeSH
• chromatografie afinitní metody   MeSH
• kaseiny metabolismus   MeSH
• krevní proteiny analýza   izolace a purifikace   metabolismus   MeSH
• kyseliny polymethakrylové chemie   MeSH
• lidé MeSH
• magnety chemie   MeSH
• mikrosféry MeSH
• protinádorové látky metabolismus   MeSH
• rekombinantní proteiny metabolismus   MeSH
• spektrometrie hmotnostní - ionizace laserem za účasti matrice metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• kaseiny MeSH
• krevní proteiny MeSH
• kyseliny polymethakrylové MeSH
• lactaptin, human MeSH Prohlížeč
• polyglycidyl methacrylate MeSH Prohlížeč
• protinádorové látky MeSH
• rekombinantní proteiny MeSH

The aim of the present study was to investigate the suitability of insoluble Eudragit® water dispersions (NE, NM, RL, and RS) for direct high-shear granulation of very soluble levetiracetam in order to decrease its burst effect from HPMC K100M matrices. The process characteristics, ss-NMR analysis, in vitro dissolution behavior, drug release mechanism and kinetics, texture profile analysis of the gel layer, and PCA analysis were explored. An application of water dispersions directly on levetiracetam was feasible only in a multistep process. All prepared formulations exhibited a 12-hour sustained release profile characterized by a reduced burst effect in a concentration-dependent manner. No effect on swelling extent of HPMC K100M was observed in the presence of Eudragit®. Contrary, higher rigidity of formed gel layer was observed using combination of HPMC and Eudragit®. Not only the type and concentration of Eudragit®, but also the presence of the surfactant in water dispersions played a key role in the dissolution characteristics. The dissolution profile close to zero-order kinetic was achieved from the sample containing levetiracetam directly granulated by the water dispersion of Eudragit® NE (5% of solid polymer per tablet) with a relatively high amount of surfactant nonoxynol 100 (1.5%). The initial burst release of drug was reduced to 8.04% in 30 min (a 64.2% decrease) while the total amount of the released drug was retained (97.02%).

• MeSH
• deriváty hypromelózy * chemie   farmakokinetika   farmakologie   MeSH
• kyseliny polymethakrylové * chemie   farmakokinetika   farmakologie   MeSH
• laktosa analogy a deriváty   chemie   farmakokinetika   farmakologie   MeSH
• léky s prodlouženým účinkem farmakokinetika   farmakologie   MeSH
• methylcelulosa analogy a deriváty   chemie   farmakokinetika   farmakologie   MeSH
• nonoxynol * chemie   farmakokinetika   farmakologie   MeSH
• uvolňování léčiv MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• deriváty hypromelózy * MeSH
• hydroxypropylmethylcellulose-lactose matrix MeSH Prohlížeč
• kyseliny polymethakrylové * MeSH
• laktosa MeSH
• léky s prodlouženým účinkem MeSH
• methylcelulosa MeSH
• methylmethacrylate-methacrylic acid copolymer MeSH Prohlížeč
• nonoxynol * MeSH

A procedure for the preparation of copolymers bearing sulfobetaine and carboxybetaine methacrylic-based monomers by free-radical polymerization is described and discussed. A combination of monomers affects the upper critical solution temperature (UCST) in water and in the presence of a simple NaCl electrolyte while retaining the zwitterionic character. In addition, hydrogel samples were prepared and showed tunable water structure and mechanical properties. The total nonfreezable water content decreases with the amount of carboxybetaine segment in the hydrogel feed and the compression moduli were in a range of 0.7-1.6 MPa. Responses to external conditions such as temperature and ion strength were investigated and a potential application such as modulated thermal detection is proposed. The presence of the carboxylate group in the carboxybetaine segment enables a small fluorescence probe and peptide bearing RDG motif to be attached to polymer and hydrogel samples, respectively. The hydrogel samples functionalized with the RGD motif exhibit controlled cell adhesion. Such synthetic strategy based on combination of different zwitterionic segments offers a simple pathway for the development of zwitterionic materials with programmable properties.

• MeSH
• betain analogy a deriváty   chemie   MeSH
• buněčná adheze účinky léků   MeSH
• buňky 3T3 MeSH
• hydrogely chemická syntéza   chemie   farmakologie   MeSH
• koncentrace vodíkových iontů MeSH
• kyseliny polymethakrylové chemická syntéza   chemie   farmakologie   MeSH
• myši MeSH
• osmolární koncentrace MeSH
• polymerizace MeSH
• tranzitní teplota MeSH
• viskoelastické látky chemická syntéza   chemie   farmakologie   MeSH
• voda chemie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• betain MeSH
• hydrogely MeSH
• kyseliny polymethakrylové MeSH
• sulfobetaine MeSH Prohlížeč
• viskoelastické látky MeSH
• voda MeSH

A water-soluble polymer cancerostatic actively targeted against cancer cells expressing a disialoganglioside antigen GD2 was designed, synthesized and characterized. A polymer conjugate of an antitumor drug doxorubicin with a N-(2-hydroxypropyl)methacrylamide-based copolymer was specifically targeted against GD2 antigen-positive tumor cells using a recombinant single chain fragment (scFv) of an anti-GD2 monoclonal antibody. The targeting protein ligand was attached to the polymer-drug conjugate either via a covalent bond between the amino groups of the protein using a traditional nonspecific aminolytic reaction with a reactive polymer precursor or via a noncovalent but highly specific interaction between bungarotoxin covalently linked to the polymer and the recombinant scFv modified with a C-terminal bungarotoxin-binding peptide. The GD2 antigen binding activity and GD2-specific cytotoxicity of the targeted noncovalent polymer-scFv complex proved to be superior to the covalent polymer-scFv conjugate.

• MeSH
• bungarotoxiny chemie   MeSH
• buňky 3T3 MeSH
• doxorubicin aplikace a dávkování   chemie   farmakologie   MeSH
• gangliosidy imunologie   MeSH
• jednořetězcové protilátky chemie   imunologie   MeSH
• kyseliny polymethakrylové chemie   MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nanokonjugáty chemie   MeSH
• proliferace buněk účinky léků   MeSH
• protinádorové látky aplikace a dávkování   chemie   farmakologie   MeSH
• vazba proteinů MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• bungarotoxiny MeSH
• doxorubicin MeSH
• Duxon MeSH Prohlížeč
• ganglioside, GD2 MeSH Prohlížeč
• gangliosidy MeSH
• jednořetězcové protilátky MeSH
• kyseliny polymethakrylové MeSH
• nanokonjugáty MeSH
• protinádorové látky MeSH

This review focuses on the characterization of (meth)acrylate copolymers - Eudragit®, describing their thermal treatment behaviour, possible interactions between cationic and anionic polymers, incompatibilities related to Eudragits® and their use in the pharmaceutical technology of oral tablets. In summary, Eudragit® copolymers are divided into soluble ones, insoluble ones and a combination of these two types. The combination of soluble and insoluble poly(meth)acrylate gave a new type of polymer, Eudragit® FL. In oral tablet technology, Eudragits® are widely used in matrix tablets, either alone or in combination, where they mainly provide sustained drug release. To a lesser extent, Eudragits® are used in gastroretentive systems. Moreover, Eudragits® are also of great importance in coated tablets technology, where these enteric polymers provide specific drug targeting to certain parts of the digestive tract, mainly to the small intestine or colon. Important systems such as CODESTM and MMX® technology are mentioned. Last but not least an overview table of currently available oral medicinal products on the Czech market, where at least one of the Eudragits® was used as a film-forming agent, is included.

• Klíčová slova
• Eudragit®, acidoresistant tablets, burst effect, colon drug delivery, film-coating tablets, floating tablets, matrix tablets, prolonged drug release,
• MeSH
• farmaceutická chemie * MeSH
• kyseliny polymethakrylové chemie   MeSH
• léky s prodlouženým účinkem MeSH
• rozpustnost MeSH
• tablety * MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• kyseliny polymethakrylové MeSH
• léky s prodlouženým účinkem MeSH
• methylmethacrylate-methacrylic acid copolymer MeSH Prohlížeč
• tablety * MeSH

Identifying protein targets of bioactive small molecules often requires complex, lengthy development of affinity probes. We present a method for stochastic modification of small molecules of interest with a photoactivatable phenyldiazirine linker. The resulting isomeric mixture is conjugated to a hydrophilic copolymer decorated with biotin and a fluorophore. We validated this approach using known inhibitors of several medicinally relevant enzymes. At least a portion of the stochastic derivatives retained their binding to the target, enabling target visualization, isolation, and identification. Moreover, the mix of stochastic probes could be separated into fractions and tested for binding affinity. The structure of the active probe could be determined and the probe resynthesized to improve binding efficiency. Our approach can thus enable rapid target isolation, identification, and visualization, while providing information required for subsequent synthesis of an optimized probe.

• MeSH
• afinitní značky chemická syntéza   chemie   účinky záření   MeSH
• aspartátové endopeptidasy antagonisté a inhibitory   chemie   MeSH
• biotin chemie   MeSH
• diazomethan analogy a deriváty   chemická syntéza   účinky záření   MeSH
• endopeptidasy MeSH
• fluoresceiny chemie   MeSH
• fluorescenční barviva chemie   MeSH
• glutamátkarboxypeptidasa II antagonisté a inhibitory   chemie   MeSH
• hmotnostní spektrometrie metody   MeSH
• inhibitory enzymů chemická syntéza   chemie   účinky záření   MeSH
• konfokální mikroskopie metody   MeSH
• kyseliny polymethakrylové chemie   MeSH
• lidé MeSH
• membránové proteiny antagonisté a inhibitory   chemie   MeSH
• nádorové buněčné linie MeSH
• proteomika metody   MeSH
• serinové endopeptidasy chemie   MeSH
• ultrafialové záření MeSH
• želatinasy antagonisté a inhibitory   chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• afinitní značky MeSH
• aspartátové endopeptidasy MeSH
• biotin MeSH
• diazomethan MeSH
• Duxon MeSH Prohlížeč
• endopeptidasy MeSH
• fibroblast activation protein alpha MeSH Prohlížeč
• fluoresceiny MeSH
• fluorescenční barviva MeSH
• glutamátkarboxypeptidasa II MeSH
• inhibitory enzymů MeSH
• kyseliny polymethakrylové MeSH
• membránové proteiny MeSH
• serinové endopeptidasy MeSH
• želatinasy MeSH