Degradable polymers
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Práce se zabývá značením prasečího insulinu techneciem( 99m Tc). Při přípravě tohoto peptidu bylopro jeho označení použito nerozpustného redox polymeru na bázi zesítěného dextranu (RP G25-IDA).Připravené kity byly označeny 99m Tc s vysokou účinností (více než 95 %) a stabilitou, které sehodnotily chromatografickými metodami. Biodistribuce 99m Tc-insulinu u potkanů s experimentálněvyvolaným diabetem v porovnání s kontrolní skupinou nevykazovala specifické hromadění značenélátky v některém z orgánů. Použitá metoda přípravy kitu i jeho značení jsou šetrné, metodou HPLCa S.E.C. nebyly nalezeny žádné degradační produkty insulinu a jeho obsah vyhovoval požadavkůmČL 97. Jedná se o první označení insulinu techneciem( 99m Tc) a rovněž o první použití redoxpolymeru pro tento účel.
The paper describes a method for porcine insulin labelling with technetium ( 99m Tc). When preparingthis peptide, an insoluble redox polymer on the basis of cross-linked dextran (RP G25-IDA) was usedfor labelling. The prepared kits were labelled with 99m Tc with a high labelling efficiency (more than95 %) and stability, as assessed using methods of chromatography. 99m Tc-insulin biodistribution inrats with experimentally induced diabetes – compared with a control group – did not demonstratespecific accumulation of the labelled substance in any organ. The method for kit preparation andits labelling are mild, HPLC and SEC did not reveal any products of insulin degradation and insulincontent met the standards of Ph.B. 97. This is the first case of insulin labelling with techne-tium( 99 Tc) and, also, the first use of a redox polymer for this purpose.
The review introduces potential advantages and limitations of applications of stimuli-responsive polymers for delivery of drugs, radionuclides and genes. Special emphasis is put on pH- and redox-responsive systems. Virusinspired systems combining pH-responsivity and reductive degradability are especially promising in the delivery of substances bioactive in the cells.
- MeSH
- chemické jevy * MeSH
- farmaceutická technologie MeSH
- fyzikální chemie MeSH
- koncentrace vodíkových iontů MeSH
- lékové transportní systémy * MeSH
- léky s prodlouženým účinkem * MeSH
- lidé MeSH
- nosiče léků * MeSH
- polymery chemie metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
Novel star polymers based on the water-soluble N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer and cyclodextrin were synthesized and the physico-chemical behavior of these precursors was studied. Semitelechelic HPMA copolymers were grafted onto the cyclodextrin core, thus forming star-like structure. Both prepared systems were designed as possible polymer carriers for the controlled release of cytostatic drugs, which after the drug release and degradation will be eliminated from the organism. Two synthesis approaches were used to obtain similar polymer carriers with different degradation rates. All the polymers were prepared by reversible addition-fragmentation chain-transfer polymerization, which guarantees low dispersity of the prepared systems.
A new thermoresponsive system designed for local radiotherapy has been developed. In this system a radionuclide complex is entrapped in a thermoresponsive polymer locally precipitated at body temperature after injection of a polymer-complex solution into the tissue where a therapeutic effect is required. The lifetime of the system is controlled by the rate of polymer hydrolysis, its dissolution and elimination from the body. The thermoresponsive polymer with the cloud temperature (CT) below body temperature is based on copolymers of N-isopropylmethacrylamide with a methacrylamide-type comonomer containing hydrophobic n-alkyls of three different sizes (C(3), C(6) and C(12)) bonded by a hydrolytically labile hydrazone bond. Hydrolysis of hydrazone bond results in a copolymer soluble at body temperature. The copolymer containing 27.5 mole% of the comonomer with the C(6) moiety, which was chosen for further study, has the CT 22 degrees C and its phase separation is complete at 34 degrees C. Polymer dissolution is complete within 48 h at both pH 5.0 or 7.4. The model therapeutic radionuclide, (64)Cu, in the form of its hydrophobic chelate bis(quinolin-8-olato-N,O) [(64)Cu]copper, is efficiently kept hydrophobically entrapped in the phase-separated polymer until the dissolution by hydrolytic degradation is completed.
This work provides a brief overview of synthetic (biosynthetic) biodegradable polymeric substances used in biomedical applications. Some of them have been used for many years, others are less known and still others are being studied and included in common use. The research and development of these biodegradable materials seeks to integrate them into the largest possible spectrum of dosage forms where degradation is desirable. In addition to one of the first established synthetic biodegradable polymers, that is, those of lactic acid, glycol and their copolymers, the group of polyanhydrides is extensively studied for the use in the pharmaceutical industry and was approved by the US FDA. Polyurethanes have achieved a wide application in orthopedic applications, bone tissue engineering and oncological indications. A great potential of immunostimulating polyphosphazenes predestines them as a new alternative for vaccine administration. Interestingly, there is a relatively new way of production of bacterial polyesters (polyhydroxyalkanoates) with a great potential in pharmaceutical and medical applications.
In order to create a soft tissue surplus, implantable volume expanders are often utilized in dental surgery. Implanted tissue expanders should gradually increase their volume, exerting a constant pressure on the surrounding tissue for weeks. Current tissue expanders are based predominantly on externally inflatable balloons or on osmotically active tissue expanders that use soft hydrogels wrapped in perforated plastic coatings, which limit fluid entry and swelling. We have designed and examined tissue expanders based on the controlled rate expansive hydrogels synthesized from copolymers of selected methacrylates and N-vinylpyrrolidone, cross-linked with a combination of non-degradable (glycol dimethacrylates) and hydrolytically degradable (N,O-dimethacryloylhydroxylamine) cross-linkers. These copolymers have close-to-linear volume expansion rates (up to 6-9 times their original volume) and exert an increasing swelling pressure in vitro. The anesthetic benzocaine has been incorporated into the hydrogels, and kinetic release experiments have shown that most of the drug (90%) was released within 48 h. Our proposed hydrogel expanders are homogeneous and have suitable mechanical properties, thus simplifying the surgical manipulations required. Further studies will be needed to completely evaluate their biocompatibility and tissue response to the implants.
- MeSH
- anestetika aplikace a dávkování MeSH
- biokompatibilní materiály chemie MeSH
- hydrogely chemie MeSH
- hydroxylaminy chemie MeSH
- kinetika MeSH
- lidé MeSH
- methakryláty chemie MeSH
- polymery chemie MeSH
- reagencia zkříženě vázaná chemie MeSH
- stomatologie metody MeSH
- tkáňové expandéry * MeSH
- tlak MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Adenovirus type 5 (Ad5) gene therapy vectors require protection against antibodies, complement proteins and blood cells if they are to be delivered intravenously to treat metastatic disease. Such protection can be achieved by chemically modifying Ad5 with polymers based on hydrophilic HPMA. Here, such polymers were designed to include side chains bearing reactive carbonyl thiazolidine-2-thione groups (TTs) to covalently modify available amino groups of the lysine residues in the Ad5 capsid. Furthermore, the inclusion of side chains bearing positively charged quaternary ammonium groups (QAs) was designed to improve electrostatic interaction of the polymers with negatively charged Ad5 hexon protein. Finally, to enable triggered uncoating and reactivation of the Ad5, either the TTs or both the TTs and the QAs were linked to polymer backbone via reductively degradable disulfide bonds. SDS-PAGE demonstrated that these polymers covalently modified Ad5 capsid proteins in a reduction reversible manner. In infection studies, polymers containing QAs prevented binding of coagulation factor X to Ad5. Furthermore, the antibody and complement mediated binding of Ad5 to erythrocytes was reduced by such polymers (>95% without polymer, 25% following coating). These data indicate that coating Ad5 therapeutics with such polymers will improve blood circulation half-life and deposition at disease sites.
- MeSH
- Adenoviridae fyziologie genetika klasifikace MeSH
- adenovirové infekce prevence a kontrola MeSH
- aminy chemie MeSH
- barvení stříbrem MeSH
- erytrocyty metabolismus MeSH
- faktor IX metabolismus MeSH
- genetická terapie MeSH
- genetické vektory MeSH
- imunologické faktory metabolismus MeSH
- komplement metabolismus MeSH
- lidé MeSH
- luciferasy metabolismus MeSH
- molekulární struktura MeSH
- molekulová hmotnost MeSH
- nádorové buněčné linie MeSH
- polymery chemická syntéza chemie MeSH
- protilátky metabolismus MeSH
- statická elektřina MeSH
- vazba proteinů MeSH
- virové plášťové proteiny chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
Bio-degradable stents are be made of different synthetic polymers (like polylactide or polyglycolide) or their co-polymers (polydioxanone). They can be used for treating benign stenoses of the small and large intestine, particularly in Crohn's disease. Endoscopic introduction of bio-degradable stents into small and large intestinal stenoses is feasible and relatively simple. Initial results are encouraging and the complication rate is low. However, there are still some difficulties that need to be overcome. The rate of early stent migration is still rather high (up to one third of patients). This might be solved by changes in the shape or rigidity of the stents as well as by further improvement in the design. Proof of long-term efficacy and safety requires further studies.
- MeSH
- biokompatibilní materiály MeSH
- Crohnova nemoc chirurgie komplikace MeSH
- dospělí MeSH
- gastrointestinální endoskopie MeSH
- lidé MeSH
- polymery MeSH
- stenty MeSH
- střevní obstrukce MeSH
- vstřebatelné implantáty MeSH
- zvířata MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
