The adhesive systems have the function to establish the connection between the restorative material and dental tissue, therefore it is of fundamental importance, because failures in the adhesive interface can reduce the life of a dental restoration. This study investigated the possibility of using the adhesive layer as a chlorhexidine modified release system evaluating their impact on the properties of these systems as well as evaluating the impact of these systems on immediate and post-aging dentin adhesion. Were used a matrix with BisGMA, UDMA, HEMA and TEGDMA copolymer and clay particles (Dellite 67G); associated with a chlorhexidine and a camphorquinone photoinitiator system. The properties of these systems were evaluated by the XRD, FTIR spectrophotometer, flexural strength, elasticity modulus, drug release, enzymatic inhibition and dentin adhesion resistance. The presence of the clay can raise the mechanical properties of the adhesive systems engendering a more resistant hybrid layer and led to a more sustained release of chlorhexidine in the systems, allowing a longer effective period of MMP-2 inhibition. The hypothesis that the addition of clays as release modulators could increase the effectiveness of these drugs in inhibiting the dentin's MPPs and consequently enhancing the adhesive durability was confirmed. These results indicate that the controlled release of chlorhexidine is able to reduce the process of loss of adhesion presenting itself as a promising system to increase the longevity of dental restorations.
- MeSH
- biokompatibilní materiály MeSH
- časové faktory MeSH
- chlorhexidin chemie MeSH
- dentin chemie MeSH
- dentinová adheziva MeSH
- jíl chemie MeSH
- léky s prodlouženým účinkem MeSH
- pevnost v tahu MeSH
- testování materiálů MeSH
- uvolňování léčiv * MeSH
- zubní materiály * MeSH
- Publikační typ
- časopisecké články MeSH
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.
- 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
The success of chemotherapy is limited by poor selectivity of active drugs combined with occurrence of tumor resistance. New star-like structured N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-based drug delivery systems containing doxorubicin attached via a pH-sensitive hydrazone bond were designed and investigated for their ability to overcome chemotherapy resistance. These conjugates combine two strategies to achieve a high drug concentration selectively at the tumor site: (I) high accumulation by passive tumor targeting based on enhanced permeability and retention effect and (II) pH-sensitive site-specific drug release due to an acidic tumor microenvironment. Mice bearing doxorubicin-resistant xenograft tumors were treated with doxorubicin, PBS, poly HPMA (pHPMA) precursor or pHPMA-doxorubicin conjugate at different equivalent doses of 5 mg/kg bodyweight doxorubicin up to a 7-fold total dose using different treatment schedules. Intratumoral drug accumulation was analyzed by fluorescence imaging utilizing intrinsic fluorescence of doxorubicin. Free doxorubicin induced significant toxicity but hardly any tumor-inhibiting effects. Administering at least a 3-fold dose of pHPMA-doxorubicin conjugate was necessary to induce a transient response, whereas doses of about 5- to 6-fold induced strong regressions. Tumors completely disappeared in some cases. The onset of response was differential delayed depending on the tumor model, which could be ascribed to distinct characteristics of the microenvironment. Further fluorescence imaging-based analyses regarding underlying mechanisms of the delayed response revealed a related switch to a more supporting intratumoral microenvironment for effective drug release. In conclusion, the current study demonstrates that the concept of tumor site-restricted high-dose chemotherapy is able to overcome therapy resistance. Mol Cancer Ther; 15(5); 998-1007. ©2016 AACR.
- MeSH
- chemorezistence * MeSH
- koncentrace vodíkových iontů * MeSH
- lékové transportní systémy * MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nosiče léků * MeSH
- polymery * MeSH
- protinádorové látky aplikace a dávkování MeSH
- uvolňování léčiv * MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- xenogenní modely - testy protinádorové aktivity MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Non-thermal plasma has been recognized as a promising tool across a vast variety of biomedical applications, with the potential to create novel therapeutic methods. However, the understanding of the molecular mechanisms behind non-thermal plasma cellular effects remains a significant challenge. In this study, we show how two types of different non-thermal plasmas induce cell death in mammalian cell cultures via the formation of multiple intracellular reactive oxygen/nitrogen species. Our results showed a discrepancy in the superoxide accumulation and lysosomal activity in response to air and helium plasma, suggesting that triggered signalling cascades might be grossly different between different plasmas. In addition, the effects of ozone, a considerable component of non-thermal plasma, have been simultaneously evaluated and have revealed much faster and higher cytotoxic effects. Our findings offer novel insight into plasma-induced cellular responses, and provide a basis for better controlled biomedical applications.
- MeSH
- acetylcystein farmakologie MeSH
- annexin A5 MeSH
- antioxidancia farmakologie MeSH
- buněčná smrt účinky léků MeSH
- buňky 3T3 MeSH
- helium chemie MeSH
- krysa rodu rattus MeSH
- lyzozomy účinky léků MeSH
- membránový potenciál mitochondrií účinky léků MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- neuroglie cytologie účinky léků metabolismus MeSH
- ozon chemie MeSH
- plazmové plyny farmakologie MeSH
- reaktivní formy dusíku agonisté antagonisté a inhibitory metabolismus MeSH
- reaktivní formy kyslíku agonisté antagonisté a inhibitory metabolismus MeSH
- signální transdukce MeSH
- viabilita buněk účinky léků MeSH
- vzduch MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
