Polyester-based nanostructures are widely studied as drug-delivery systems due to their biocompatibility and biodegradability. They are already used in the clinic. In this work, we describe a new and simple biodegradable and biocompatible system as the Food and Drug Administration approved polyesters (poly-ε-caprolactone, polylactic acid, and poly(lactic- co-glycolic acid)) for the delivery of the anticancer drug paclitaxel (PTX) as a model drug. A hydrophobic polyester, poly(propylene succinate) (PPS), was prepared from a nontoxic alcohol (propylene glycol) and monomer from the Krebs's cycle (succinic acid) in two steps via esterification and melt polycondensation. Furthermore, their amphiphilic block copolyester, poly(ethylene oxide monomethyl ether)- block-poly(propylene succinate) (mPEO- b-PPS), was prepared by three steps via esterification followed by melt polycondensation and the addition of mPEO to the PPS macromolecules. Analysis of the in vitro cellular behavior of the prepared nanoparticle carriers (NPs) (enzymatic degradation, uptake, localization, and fluorescence resonance energy-transfer pair degradation studies) was performed by fluorescence studies. PTX was loaded to the NPs of variable sizes (30, 70, and 150 nm), and their in vitro release was evaluated in different cell models and compared with commercial PTX formulations. The mPEO- b-PPS copolymer analysis displays glass transition temperature < body temperature < melting temperature, lower toxicity (including the toxicity of their degradation products), drug solubilization efficacy, stability against spontaneous hydrolysis during transport in bloodstream, and simultaneous enzymatic degradability after uptake into the cells. The detailed cytotoxicity in vitro and in vivo tumor efficacy studies have shown the superior efficacy of the NPs compared with PTX and PTX commercial formulations.

• MeSH
• micely MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nanočástice škodlivé účinky   chemie   metabolismus   MeSH
• paclitaxel aplikace a dávkování   farmakokinetika   MeSH
• polyestery chemická syntéza   chemie   MeSH
• polyethylenglykoly chemie   MeSH
• polypropyleny chemie   MeSH
• protinádorové látky aplikace a dávkování   farmakokinetika   MeSH
• sukcináty chemie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

To minimize non-specific protein adsorption on macroporous poly(glycidyl methacrylate) and poly(2-hydroxyethyl methacrylate) microspheres containing amino and/or carboxyl groups, the microspheres are coated with α,ω-bis-carboxy poly(ethylene glycol) and amino-terminated poly(ethylene glycol-co-propylene glycol) or α-methoxy-ω-amino poly(ethylene glycol). Adsorption of bovine serum albumin (BSA), γ-globulin, (125) I-BSA, pepsin, and chymotrypsin on neat and PEGylated microspheres is determined by UV-VIS spectroscopy of supernatants and eluates or by measurement of radioactivity in an ionization chamber. Neat and PEGylated microspheres adsorb 0.8-70% and 0.02-44% of protein, respectively.

• MeSH
• adsorpce MeSH
• biotechnologie metody   MeSH
• chymotrypsin chemie   MeSH
• gama-globuliny chemie   MeSH
• kyseliny polymethakrylové chemie   MeSH
• mikrosféry * MeSH
• molekulární struktura MeSH
• polyethylenglykoly chemie   MeSH
• polyhydroxyethylmethakrylát chemie   MeSH
• radioizotopy jodu chemie   MeSH
• sérový albumin hovězí chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Poly(2-alkenyl-2-oxazoline)s are promising functional polymers for a variety of biomedical applications, such as drug delivery systems, peptide conjugates, or gene delivery. In this study, poly(2-isopropenyl-2-oxazoline) (PIPOx) is prepared through free-radical polymerization initiated with azobisisobutyronitrile. Reactive 2-oxazoline units in the side chain support an addition reaction with different compounds containing a carboxylic group, which facilitates the preparation of polymers labeled with two different fluorescent dyes. The cytotoxicities of 2-oxazoline monomers, PIPOx, and fluorescently labeled PIPOx are evaluated in vitro using an 3-(4,5-Dimethyldiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and ex vivo using a cell proliferation assay with adenosine triphosphate bioluminescence. The cell uptake of labeled PIPOx is used to determine the colocalization of PIPOx with cell organelles that are part of the endocytic pathway. For the first time, it is shown that poly(2-isopropenyl-2-oxazoline) is a biocompatible material and is suitable for biomedical applications; further, its immunomodulative properties are evaluated.

• MeSH
• biokompatibilní materiály chemická syntéza   chemie   farmakologie   MeSH
• buněčná smrt účinky léků   MeSH
• buňky 3T3 MeSH
• endocytóza účinky léků   MeSH
• fibroblasty cytologie   MeSH
• fluorescenční spektrometrie MeSH
• imunomodulace účinky léků   MeSH
• konfokální mikroskopie MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• organely účinky léků   metabolismus   MeSH
• oxazoly chemická syntéza   chemie   farmakologie   MeSH
• polymery chemická syntéza   chemie   farmakologie   MeSH
• polypropyleny chemická syntéza   chemie   farmakologie   MeSH
• proliferace buněk účinky léků   MeSH
• slezina cytologie   MeSH
• viabilita buněk účinky léků   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• Klíčová slova
• Neusilin, liquisolid systémy,
• MeSH
• biologická dostupnost * MeSH
• enterosolventní tablety MeSH
• farmaceutická chemie * MeSH
• farmaceutické pomocné látky MeSH
• hydrofobní a hydrofilní interakce MeSH
• nosiče léků MeSH
• polyethylenglykoly MeSH
• příprava léků * MeSH
• propylenglykol MeSH
• rosuvastatin kalcium * MeSH
• rozpustnost MeSH
• silikáty MeSH
• sloučeniny hliníku MeSH
• sloučeniny hořčíku MeSH
• tobolky MeSH
• Publikační typ
• hodnotící studie MeSH

A new targeted intravenous conjugate of nystatin with pentaerythritol poly(ethylene glycol)ether has been prepared and characterised (NY(4)-sPEG, M=25 160). The conjugate contains a beta-d-glucopyranoside molecular switch sensitive to beta-glucosidases (E.C.3.2.1.21), which are specifically present in the enzyme outfit of fungal pathogens. The investigated conjugate is stable under in vitro conditions for 24h (solution of phosphate buffer pH=7.4). Spectrophotometrically controlled releasing of nystatin in model medium containing beta-glucosidase ((Aspergillus niger) 2mg/mL, 66.6 units/g; pH 7.4, 2 x 10(-2)M), reported decomposition half-life of conjugate tau(1/2)=(88+/-2)s. This implies that releasing of nystatin is controlled only enzymatically.

• MeSH
• antifungální látky aplikace a dávkování   chemie   metabolismus   MeSH
• Aspergillus niger enzymologie   MeSH
• celulasy izolace a purifikace   metabolismus   MeSH
• farmaceutická chemie MeSH
• farmaceutická technologie metody   MeSH
• gelová chromatografie MeSH
• hydrolýza MeSH
• kinetika MeSH
• koncentrace vodíkových iontů MeSH
• léky s prodlouženým účinkem MeSH
• magnetická rezonanční spektroskopie MeSH
• nosiče léků MeSH
• nystatin aplikace a dávkování   chemie   metabolismus   MeSH
• poločas MeSH
• polyethylenglykoly chemie   MeSH
• příprava léků MeSH
• propylenglykoly chemie   MeSH
• pufry MeSH
• rozpustnost MeSH
• spektrofotometrie ultrafialová MeSH
• stabilita léku MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Syntézu kolagenu studují autoři ve vztahu k intermediárnímu metabolismu a k vlivům aminokyselin, zvláště prolinu a jeho analogů. Důvodem k tomu je, že ovlivnění tvorby kolagenu souvisí s podmínkami mechanismu vzniku hydroxyprolinu, který spolu s hydroxylysinem tvoří dvě aminokyseliny obsažené v kolagenu. Publikace se dále zabývá vlivem kovů a chelátotvorných látek na syntézu a metabolismus kolagenu. Věnuje pozornost atypickému kolagenu,protokolagen-hydroxylase a vlivu kyseliny askorbové a parciálního tlaku kyslíku na syntézu kolagenu. Z látek zasahujících do tvorby kolagenu uvádí polyvinylpyridin- N-oxid, oligo-N-metyl-morfolinium-propylen-oxid atetrahydroxychinon; Syntézu kolagenu studují autoři ve vztahu k intermediárnímu metabolismu a k vlivům aminokyselin, zvláště prolinu a jeho analogů. Důvodem k tomu je, že ovlivnění tvorby kolagenu souvisí s podmínkami mechanismu vzniku hydroxyprolinu, který spolu s hydroxylysinem tvoří dvě aminokyseliny obsažené v kolagenu. Publikace se dále zabývá vlivem kovů a chelátotvorných látek na syntézu a metabolismus kolagenu. Věnuje pozornost atypickému kolagenu, protokolagen-hydroxylase a vlivu kyseliny askorbové a parciálního tlaku kyslíku na syntézu kolagenu. Z látek zasahujících do tvorby kolagenu uvádí polyvinylpyridin- N-oxid, oligo-N-metyl-morfolinium-propylen-oxid atetrahydroxychinon.

• MeSH
• chelátory chemie   MeSH
• hydroxylysin MeSH
• hydroxyprolin MeSH
• kolagen biosyntéza   metabolismus   MeSH
• kovy chemie   MeSH
• kyselina askorbová chemie   MeSH
• polyvinylpyridin-N-oxid chemie   MeSH

• Konspekt
• Fyziologie člověka a srovnávací fyziologie
• NLK Obory
• vnitřní lékařství
• fyziologie
• NLK Publikační typ
• studie

In this study, a sensitive platform was designed for the electrocatalytical oxidation and recognition of ascorbic acid (AA) based on poly(β-cyclodextrin) modified glassy carbon electrode (p(β-CD-GCE). Electropolymerization of β-CD on the surface of GCE was performed on the potential range of -1 to 1.5 V. So, a novel biopolymer was prepared on the surface of GCE towards sensitive recognition of AA in human plasma samples. The developed platform has good sensitivity and accuracy for electrooxidation and detection of AA with lower limit of quantification (LLOQ) of 1 nM and linear range of 1 nM to 100 mM. Moreover, the designed electrochemical sensor was employed for the analysis of AA on human plasma samples with high sensitivity. Based on advantages of p(β-CD) prepared by electropolymerization procedure (green, fast, homogeny, and efficient eletrocatalytical behaviour), this conductive biopolymer showed excellent analytical behaviour towards electrooxidation of AA. It is expected that the prepared polymeric interface is able to use in the analysis of biological species in clinical samples.

• MeSH
• beta-cyklodextriny MeSH
• biokompatibilní materiály MeSH
• biopolymery MeSH
• elektrochemické techniky * metody   MeSH
• kyselina askorbová * MeSH
• lidé MeSH
• propylenglykoly MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

The influence of maltose-modified poly(propylene imine) (PPI) dendrimers on dimyristoylphosphatidylcholine (DMPC) or dimyristoylphosphatidylcholine/dimyristoylphosphatidylglycerol (DMPC/DMPG) (3%) liposomes was studied. Fourth generation (G4) PPI dendrimers with primary amino surface groups were partially (open shell glycodendrimers - OS) or completely (dense shell glycodendrimers - DS) modified with maltose residues. As a model membrane, two types of 100nm diameter liposomes were used to observe differences in the interactions between neutral DMPC and negatively charged DMPC/DMPG bilayers. Interactions were studied using fluorescence spectroscopy to evaluate the membrane fluidity of both the hydrophobic and hydrophilic parts of the lipid bilayer and using differential scanning calorimetry to investigate thermodynamic parameter changes. Pulsed-filed gradient NMR experiments were carried out to evaluate common diffusion coefficient of DMPG and DS PPI in D2O when using below critical micelle concentration of DMPG. Both OS and DS PPI G4 dendrimers show interactions with liposomes. Neutral DS dendrimers exhibit stronger changes in membrane fluidity compared to OS dendrimers. The bilayer structure seems more rigid in the case of anionic DMPC/DMPG liposomes in comparison to pure and neutral DMPC liposomes. Generally, interactions of dendrimers with anionic DMPC/DMPG and neutral DMPC liposomes were at the same level. Higher concentrations of positively charged OS dendrimers induced the aggregation process with negatively charged liposomes. For all types of experiments, the presence of NaCl decreased the strength of the interactions between glycodendrimers and liposomes. Based on NMR diffusion experiments we suggest that apart from electrostatic interactions for OS PPI hydrogen bonds play a major role in maltose-modified PPI dendrimer interactions with anionic and neutral model membranes where a contact surface is needed for undergoing multiple H-bond interactions between maltose shell of glycodendrimers and surface membrane of liposome.

• MeSH
• dendrimery chemie   metabolismus   MeSH
• difenylhexatrien chemie   MeSH
• diferenciální skenovací kalorimetrie MeSH
• dimyristoylfosfatidylcholin chemie   metabolismus   MeSH
• fluidita membrány MeSH
• fluorescenční polarizace MeSH
• fosfatidylglyceroly chemie   metabolismus   MeSH
• hydrofobní a hydrofilní interakce MeSH
• lipidové dvojvrstvy chemie   metabolismus   MeSH
• liposomy chemie   metabolismus   MeSH
• magnetická rezonanční spektroskopie MeSH
• maltosa chemie   metabolismus   MeSH
• membránové lipidy chemie   metabolismus   MeSH
• polypropyleny chemie   metabolismus   MeSH
• statická elektřina MeSH
• vodíková vazba MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

New amphiphilic diblock polymer nanotherapeutics serving simultaneously as a drug delivery system and an inhibitor of multidrug resistance were designed, synthesized, and evaluated for their physico-chemical and biological characteristics. The amphiphilic character of the diblock polymer, containing a hydrophilic block based on the N-(2-hydroxypropyl)methacrylamide copolymer and a hydrophobic poly(propylene oxide) block (PPO), caused self-assembly into polymer micelles with an increased hydrodynamic radius (Rhof approximately 15nm) in aqueous solutions. Doxorubicin (Dox), as a cytostatic drug, was bound to the diblock polymer through a pH-sensitive hydrazone bond, enabling prolonged circulation in blood, the delivery of Dox into a solid tumor and the subsequent stimuli-sensitive controlled release within the tumor mass and tumor cells at a decreased pH. The applicability of micellar nanotherapeutics as drug carriers was confirmed by an in vivo evaluation using EL4 lymphoma-bearing C57BL/6 mice. We observed significantly higher accumulation of micellar conjugates in a solid tumor because of the EPR effect compared with similar polymer-drug conjugates that do not form micellar structures or with the parent free drug. In addition, highly increased anti-tumor efficacy of the micellar polymer nanotherapeutics, even at a sub-optimal dose, was observed. The presence of PPO in the structure of the diblock polymer ensured, during in vitro tests on human and mouse drug-sensitive and resistant cancer cell lines, the inhibition of P-glycoprotein, one of the most frequently expressed ATP-dependent efflux pump that causes multidrug resistance. In addition, we observed highly increased rate of the uptake of the diblock polymer nanotherapeutics within the cells. We suppose that combination of unique properties based on MDR inhibition, stimuli sensitiveness (pH sensitive activation of drug), improved pharmacokinetics and increased uptake into the cells made the described polymer micelle a good candidate for investigation as potential drug delivery system.

• MeSH
• akrylamidy aplikace a dávkování   chemie   farmakokinetika   terapeutické užití   MeSH
• chemorezistence účinky léků   MeSH
• doxorubicin aplikace a dávkování   chemie   farmakokinetika   terapeutické užití   MeSH
• hydrofobní a hydrofilní interakce MeSH
• lidé MeSH
• micely * MeSH
• mnohočetná léková rezistence účinky léků   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nádory farmakoterapie   metabolismus   patologie   MeSH
• nosiče léků aplikace a dávkování   chemie   farmakokinetika   terapeutické užití   MeSH
• polymery aplikace a dávkování   chemie   farmakokinetika   terapeutické užití   MeSH
• propylenglykoly aplikace a dávkování   chemie   farmakokinetika   terapeutické užití   MeSH
• protinádorová antibiotika aplikace a dávkování   chemie   farmakokinetika   terapeutické užití   MeSH
• tumor burden účinky léků   MeSH
• uvolňování léčiv MeSH
• viabilita buněk účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• Publikační typ
• příručky MeSH

• Konspekt
• Chemie. Mineralogické vědy
• NLK Obory
• chemie, klinická chemie