A little is known about the link between the macromolecular architecture of dialdehyde polysaccharides (DAPs), their crosslinking capabilities, and the properties of resulting hydrogels. Here, DAPs based on cellulose, dextrin, dextran, and hyaluronate were compared as crosslinkers for poly(vinyl alcohol), PVA. The swelling, network parameters, viscoelastic properties, porosity, and cytotoxicity of PVA/DAP hydrogels were investigated concerning the crosslinker structure, molecular weight, aldehyde group density per macromolecule, and the size of spontaneously formed crosslinker nano-assemblies. Generally, crosslinkers based on linear polysaccharides (cellulose, hyaluronate) performed more reliably, while the presence of branching could be both beneficial (dextran) but also detrimental (dextrin) at lower crosslinker concentrations. For example, the hydrogel swelling differed by up to one-third (600 vs. 400%) and storage modulus even by up to one half (~7000 vs. ~3500 Pa) depending on crosslinker structure and properties. These differences were rationalized by variances in crosslinking modes derived based on obtained data.
- MeSH
- buňky NIH 3T3 MeSH
- hydrogely chemie farmakologie MeSH
- myši MeSH
- polysacharidy chemie farmakologie MeSH
- polyvinylalkohol chemie farmakologie MeSH
- reagencia zkříženě vázaná chemie farmakologie MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
Study provides an in-depth analysis of the structure-function relationship of polysaccharide anticancer drug carriers and points out benefits and potential drawbacks of differences in polysaccharide glycosidic bonding, branching and drug binding mode of the carriers. Cellulose, dextrin, dextran and hyaluronic acid have been regioselectively oxidized to respective dicarboxylated derivatives, allowing them to directly conjugate cisplatin, while preserving their major structural features intact. The structure of source polysaccharide has crucial impact on conjugation effectiveness, carrier capacity, drug release rates, in vitro cytotoxicity and cellular uptake. For example, while branched structure of dextrin-based carrier partially counter the undesirable initial burst release, it also attenuates the cellular uptake and the cytotoxicity of carried drug. Linear polysaccharides containing β-(1→4) glycosidic bonds and oxidized at C2 and C3 (cellulose and hyaluronate) have the best overall combination of structural features for improved drug delivery applications including potentiation of the cisplatin efficacy towards malignances.
- MeSH
- buňky NIH 3T3 MeSH
- celulosa chemie MeSH
- cisplatina aplikace a dávkování MeSH
- dextrany chemie MeSH
- dextriny chemie MeSH
- glykosidy chemie MeSH
- inhibiční koncentrace 50 MeSH
- kyselina hyaluronová chemie MeSH
- kyslík chemie MeSH
- lékové transportní systémy * MeSH
- lidé MeSH
- MFC-7 buňky MeSH
- myši MeSH
- nosiče léků * MeSH
- oxidace-redukce MeSH
- platina chemie MeSH
- polysacharidy chemie MeSH
- protinádorové látky aplikace a dávkování MeSH
- techniky in vitro MeSH
- uvolňování léčiv MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The design of improved biopolymeric based hydrogel materials with high load-capacity to serve as biocompatible drug carriers is a challenging task with vital implications in health sciences. In this work, chitosan crosslinked dialdehyde xanthan gum interpenetrated hydroxypropyl methylcellulose gels were developed for the controlled delivery of different antibiotic drugs including ampicillin, minocycline and rifampicin. The prepared hydrogel scaffolds were characterized by rheology method, FTIR, SEM, TGA and compression analysis. In addition, gelation kinetics, swelling, in vitro degradation and drug release rate were studied under simulated gastrointestinal fluid conditions of pH 2.0 and 7.4 at 37 °C. Results demonstrated the gel composition and structure affected drug release kinetics. The release study showed more than 50% cumulative release within 24 h for all investigated antibiotic drugs. In vitro cell cytocompatibility using mouse embryonic fibroblast cell lines depicted ≥80% cell viability, indicating the gels are non-toxic. Finally, the antibacterial activity of loaded gels was evaluated against Gram-negative and positive bacteria (Escherichia coli, Staphylococcus aureus and Klebsiella pneumonia), which correlated well with swelling and drug release results. Overall, the present study demonstrated that the produced hydrogel scaffolds serves as promising material for controlled antibiotic delivery towards microbial growth inhibition.
- MeSH
- ampicilin farmakologie MeSH
- antibakteriální látky farmakologie MeSH
- bakteriální polysacharidy chemie MeSH
- biokompatibilní materiály chemie MeSH
- buněčné linie MeSH
- chitosan chemie MeSH
- deriváty hypromelózy chemie MeSH
- Escherichia coli účinky léků MeSH
- fibroblasty MeSH
- hydrogely chemická syntéza chemie farmakokinetika toxicita MeSH
- koncentrace vodíkových iontů MeSH
- mikrobiální testy citlivosti MeSH
- mikroskopie elektronová rastrovací MeSH
- minocyklin farmakologie MeSH
- myši MeSH
- nosiče léků chemie MeSH
- reologie MeSH
- rifampin farmakologie MeSH
- spektroskopie infračervená s Fourierovou transformací MeSH
- Staphylococcus aureus účinky léků MeSH
- termogravimetrie MeSH
- uvolňování léčiv MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Novel composite films combining biocompatible polysaccharides with conducting polyaniline (PANI) were prepared via the in-situ polymerization of aniline hydrochloride in the presence of sodium hyaluronate (SH) or chitosan (CH). The composite films possess very good cytocompatibility in terms of adhesion and proliferation of two lines of human induced pluripotent stem cells (hiPSC). Moreover, the cardiomyogenesis and even formation of beating clusters were successfully induced on the films. The proportion of formed cardiomyocytes demonstrated excellent properties of composites for tissue engineering of stimuli-responsive tissues. The testing also demonstrated antibacterial activity of the films against E. coli and PANI-SH was able to reduce bacterial growth from 2 × 105 to < 1 cfu cm-2. Physicochemical characterization revealed that the presence of polysaccharides did not notably influence conductivities of the composites being ∼1 and ∼2 S cm-1 for PANI-SH and PANI-CH respectively; however, in comparison with neat PANI, it modified their topography making the films smoother with mean surface roughness of 4 (PANI-SH) and 14 nm (PANI-CH). The combination of conductivity, antibacterial activity and mainly cytocompatibility with hiPSC opens wide application potential of these polysaccharide-based composites.
- MeSH
- aniliny chemie MeSH
- antibakteriální látky chemie farmakologie MeSH
- biokompatibilní materiály chemie farmakologie MeSH
- buněčná adheze účinky léků MeSH
- buněčné linie MeSH
- chitosan chemie MeSH
- elektrická vodivost MeSH
- Escherichia coli účinky léků MeSH
- indukované pluripotentní kmenové buňky účinky léků metabolismus MeSH
- kyselina hyaluronová chemie MeSH
- lidé MeSH
- nanokompozity chemie MeSH
- polymerizace MeSH
- povrchové vlastnosti MeSH
- proliferace buněk účinky léků MeSH
- Staphylococcus aureus účinky léků MeSH
- tkáňové inženýrství metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- tisková chyba MeSH
2,3-Dialdehyde cellulose (DAC) was used as an efficient and low-toxicity crosslinker to prepare thin PVA/DAC hydrogel films designed for topical applications such as drug-loaded patches, wound dressings or cosmetic products. An optimization of hydrogel properties was achieved by the variation of two factors - the amount of crosslinker and the weight-average molecular weight (Mw) of the source PVA. The role of each factor to network parameters, mechanical, rheological and surface properties, hydrogel porosity and transdermal absorption is discussed. The best results were obtained for hydrogel films prepared using 0.25 wt% of DAC and PVA with Mw = 130 kDa, which had a high porosity and drug-loading capacity (high water content), mechanical properties allowing easy handling, best adherence to the skin from all tested samples and improved transdermal drug-delivery. Hydrogel films are biocompatible, show no cytotoxicity and have no negative impact on cell growth and morphology in their presence. Furthermore, hydrogels do not support cell migration and attachment to their surface, which should ensure easy removal of hydrogel patches even from wounded or damaged skin after use.
- MeSH
- celulosa analogy a deriváty MeSH
- hydrogely MeSH
- obvazy * MeSH
- polyvinylalkohol * MeSH
- Publikační typ
- časopisecké články MeSH
Conducting polymers (CP) can be used as pH- and/or electro-responsive components in various bioapplications, for example, in 4D smart scaffolds. The ability of CP to maintain conductivity under physiological conditions is, therefore, their crucial property. Unfortunately, the conductivity of the CP rapidly decreases in physiological environment, as their conducting salts convert to non-conducting bases. One of the promising solutions how to cope with this shortcoming is the use of alternative "doping" process that is not based on the protonation of CP with acids but on interactions relying in acidic hydrogen bonding. Therefore, the phosphonates (dimethyl phosphonate, diethyl phosphonate, dibutyl phosphonate, or diphenyl phosphonate) were used to re-dope two most common representatives of CP, polyaniline (PANI) and polypyrrole (PPy) bases. As a result, PANI doped with organic phosphonates proved to have significantly better stability of conductivity under different pH. It has also been shown that cytotoxicity of studied materials determined on embryonic stem cells and their embryotoxicity, determined as the impact on cardiomyogenesis and erythropoiesis, depend both on the polymer and phosphonate types used. With the exception of PANI doped with dibutyl phosphonate, all PPy-based phosphonates showed better biocompatibility than the phosphonates based on PANI.
- MeSH
- aniliny chemie farmakologie MeSH
- biokompatibilní materiály chemie farmakologie MeSH
- buněčná diferenciace účinky léků MeSH
- buněčné linie MeSH
- elektrická vodivost MeSH
- koncentrace vodíkových iontů MeSH
- myší embryonální kmenové buňky MeSH
- myši MeSH
- organofosfonáty chemie MeSH
- polymery chemie farmakologie MeSH
- pyrroly chemie farmakologie MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The cytocompatibility of cardiomyocytes derived from embryonic stem cells and neural progenitors, which were seeded on the surface of composite films made of graphene oxide (GO) and polypyrrole (PPy-GO) or poly(3,4-ethylenedioxythiophene) (PEDOT-GO) are reported. The GO incorporated in the composite matrix contributes to the patterning of the composite surface, while the electrically conducting PPy and PEDOT serve as ion-to-electron transducers facilitating electrical stimulation/sensing. The films were fabricated by a simple one-step electropolymerization procedure on electrically conducting indium tin oxide (ITO) and graphene paper (GP) substrates. Factors affecting the cell behaviour, i.e. the surface topography, wettability, and electrical surface conductivity, were studied. The PPy-GO and PEDOT-GO prepared on ITO exhibited high surface conductivity, especially in the case of the ITO/PPy-GO composite. We found that for cardiomyocytes, the PPy-GO and PEDOT-GO composites counteracted the negative effect of the GP substrate that inhibited their growth. Both the PPy-GO and PEDOT-GO composites prepared on ITO and GP significantly decreased the cytocompatibility of neural progenitors. The presented results enhance the knowledge about the biological properties of electroactive materials, which are critical for tissue engineering, especially in context stimuli-responsive scaffolds.
- MeSH
- bicyklické sloučeniny heterocyklické chemie MeSH
- elektrická vodivost * MeSH
- elektrochemie * MeSH
- grafit farmakologie MeSH
- kardiomyocyty cytologie účinky léků MeSH
- myši MeSH
- nervové kmenové buňky cytologie účinky léků MeSH
- neurogeneze účinky léků MeSH
- polymery chemie farmakologie MeSH
- pyrroly chemie MeSH
- voda chemie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Despite great efforts, the design of antibacterial surfaces is still a challenge. In this work, results of structural, mechanical, cytotoxic and antibacterial activities of hydrophobic carbon quantum dots/polydimethylsiloxane surfaces are presented. Antibacterial action of this surface is based on the generation of reactive oxygen species which cause bacteria damage by oxidative stress. At the same time, this surface was not cytotoxic towards the NIH/3T3 cells. Swelling-encapsulation-shrink method is applied for encapsulation of hydrophobic carbon quantum dots in medical grade silicone-polydimethylsiloxane. XPS and photoluminescence spectroscopy analyses confirm that hydrophobic carbon quantum dots have been encapsulated successfully into polydimethylsiloxane polymer matrix. Based on stress-strain test the improvement of mechanical properties of these nanocomposites is established. It is shown by electron paramagnetic resonance spectroscopy and luminescence method that nanocomposite generates singlet oxygen initiated by 470 nm blue light irradiation. Antibacterial testing shows the nanocomposite in the form of foil kills Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae and is very effective after only a 15 min irradiation.
- MeSH
- dimethylpolysiloxany farmakologie MeSH
- Escherichia coli účinky léků MeSH
- fotochemoterapie metody MeSH
- Klebsiella pneumoniae účinky léků MeSH
- kvantové tečky terapeutické užití MeSH
- myši MeSH
- nanokompozity terapeutické užití MeSH
- povrchové vlastnosti MeSH
- singletový kyslík metabolismus MeSH
- Staphylococcus aureus účinky léků MeSH
- uhlík farmakologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The synthesis of selectively oxidized cellulose, 2,3-dicarboxycellulose (DCC), is optimized for preparation of highly oxidized material for biological applications, which includes control over the molecular weight of the product during its synthesis. Conjugates of DCC and cisplatin simultaneously offer a very high drug binding efficiency (>90%) and drug loading capacity (up to 50 wt %), while retaining good aqueous solubility. The adjustable molecular weight of the DCC together with variances in drug feeding ratio allows to optimize cisplatin release profiles from delayed (<2% of cisplatin released during 6 h) to classical burst release with more than 60% of cisplatin released after 24 h. The release rates are also pH-dependent (up to 2 times faster release at pH 5.5 than at pH 7.4), which allows to exploit the acidic nature of tumor microenvironment. Extensive in vitro studies were performed on eight different cell lines for two cisplatin-DCC conjugates with different release profiles. In comparison with free cisplatin, both cisplatin-DCC conjugates demonstrated considerably lower cytotoxicity toward healthy cells. Conjugates with burst release profiles were found more effective against prostate cell lines, while DCC conjugates with slower release were more cytotoxic against ovarian and lung carcinoma cell lines. In vivo studies indicated a significantly longer survival rate, a reduction in tumor volume, and a higher accumulation of platinum in tumors of mice treated with the cisplatin-DCC conjugate in comparison to those treated by free cisplatin.
- MeSH
- buňky NIH 3T3 MeSH
- buňky PC-3 MeSH
- celulosa * chemie farmakokinetika farmakologie MeSH
- cisplatina * chemie farmakokinetika farmakologie MeSH
- koncentrace vodíkových iontů MeSH
- léky s prodlouženým účinkem chemie farmakokinetika farmakologie MeSH
- lidé MeSH
- myši MeSH
- nádorové mikroprostředí účinky léků MeSH
- nádory * farmakoterapie metabolismus patologie MeSH
- oxidace-redukce MeSH
- protinádorové látky * chemie farmakokinetika farmakologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH