Většina klinicky používaných chemoterapeutik je systémově toxická, to znamená, že ovlivňují celý organismus pacienta. Nerozeznávají, jedná-li se o buňku zdravou nebo nádorovou. Mají vedlejší účinky, a tak o nich říkáme, že jsou myelotoxická, hepatotoxická, nefrotoxická a imunotoxická. Cíleně směrovaná léčiva, která jsou tvořena syntetickým polymerním nosičem, na který je navázáno léčivo a směrující struktura, působí přímo na postižené buňky, a tak tyto nežádoucí vedlejší účinky nemají.

• MeSH
• biologická terapie MeSH
• glykoproteiny MeSH
• imunotoxiny MeSH
• toxikologie MeSH
• Publikační typ
• přednášky MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• onkologie

• Publikační typ
• abstrakt z konference MeSH

• Publikační typ
• abstrakt z konference MeSH

• Publikační typ
• abstrakt z konference MeSH

Two conjugates of anticancer drug doxorubicin (Dox) covalently bound by the hydrolytically degradable hydrazone bond to the polymer carrier based on water-soluble N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers were synthesized and their properties were compared, namely their behavior in vivo. The polymer carriers differed in dispersity due to different methods of synthesis; the carrier with relatively high dispersity (HD) was prepared by free radical polymerization (Mw=29,900 g/mol, D=1.75) and the carrier with low dispersity (LD) by controlled radical polymerization (Mw=30,000 g/mol, D=1.13). Both polymer-Dox conjugates showed prolonged blood circulation and tumor accumulation of the drug in comparison with the free drug; e.g. the tumor-to-blood ratio for the polymer-bound Dox was 3-5 times higher. The LD polymer-Dox conjugate exhibited moderately higher tumor accumulation than the HD one at a dose of 1x15 mg Dox (eq.)/kg. Also, their anti-tumor activity did not differ when injected at this dose. However, the increase of the dose to 1x25 mg Dox (eq.)/kg resulted in the enhanced therapeutic activity of the conjugates, especially of the LD one with 100% of long-term survivals. The dispersity of polymer drug carriers influenced the tumor accumulation rate, which affected the overall anti-cancer activity of polymer-drug conjugates.

• MeSH
• analýza přežití MeSH
• antibiotika antitumorózní chemie   farmakokinetika   farmakologie   MeSH
• doxorubicin chemie   farmakokinetika   farmakologie   MeSH
• experimentální nádory farmakoterapie   metabolismus   patologie   MeSH
• léky s prodlouženým účinkem MeSH
• methakryláty chemie   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nosiče léků MeSH
• polymery chemická syntéza   MeSH
• tkáňová distribuce MeSH
• volné radikály chemie   MeSH
• xenogenní modely - testy antitumorózní aktivity MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

Efficient intravenous delivery is the greatest single hurdle, with most nanotherapeutics frequently found to be unstable in the harsh conditions of the bloodstream. In the case of nanotherapeutics for gene delivery, viral vectors are often avidly recognized by both the innate and the adaptive immune systems. So, most modern delivery systems have benefited from being coated with hydrophilic polymers. Self-assembling delivery systems can achieve both steric and lateral stabilization following surface coating, endowing them with much improved systemic circulation properties and better access to disseminated targets; similarly, gene delivery viral vectors can be 'stealthed' and their physical properties modulated by surface coating. Polymers that start degrading under acidic conditions are increasingly investigated as a pathway to trigger the release of drugs or genes once the carrier reaches a slightly acidic tumor environment or after the carrier has been taken up by cells, resulting in the localization of the polymer in acidic endosomes and lysosomes. Advances in the design of acid-degradable drug and gene delivery systems have been focused and discussed in this article with stress placed on HPMA-based copolymers. We designed a system that is able to "throw away" the polymer coat after successful transport of the vector into a target cell. Initial biological studies were performed and it was demonstrated that this principle is applicable for real adenoviral vectors. It was shown that the transfection ability of coated virus at pH 7.4 is 75 times lower then transfection at pH 5.4.

• MeSH
• Adenoviridae genetika   MeSH
• chemie farmaceutická * MeSH
• endozomy MeSH
• genetické vektory MeSH
• koncentrace vodíkových iontů MeSH
• lidé MeSH
• lyzozomy MeSH
• mikrosféry MeSH
• nanomedicína metody   MeSH
• polymery MeSH
• technika přenosu genů * MeSH
• transfekce MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• Publikační typ
• abstrakt z konference MeSH

• Publikační typ
• abstrakt z konference MeSH

• Publikační typ
• abstrakt z konference MeSH

• Publikační typ
• abstrakt z konference MeSH