Novel star HPMA-based polymer conjugates for passive targeting to solid tumors
Jazyk angličtina Země Anglie, Velká Británie Médium print-electronic
Typ dokumentu srovnávací studie, časopisecké články, práce podpořená grantem
- MeSH
- akrylamidy chemie MeSH
- antibiotika antitumorózní aplikace a dávkování chemie farmakokinetika MeSH
- dendrimery chemie MeSH
- doxorubicin aplikace a dávkování chemie farmakokinetika MeSH
- koncentrace vodíkových iontů MeSH
- léky s prodlouženým účinkem MeSH
- lymfom T-buněčný farmakoterapie patologie MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nosiče léků chemie MeSH
- rozpustnost MeSH
- systémy cílené aplikace léků * MeSH
- tkáňová distribuce MeSH
- voda chemie 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
- Názvy látek
- akrylamidy MeSH
- antibiotika antitumorózní MeSH
- dendrimery MeSH
- doxorubicin MeSH
- léky s prodlouženým účinkem MeSH
- N-(2-hydroxypropyl)methacrylamide MeSH Prohlížeč
- nosiče léků MeSH
- PAMAM Starburst MeSH Prohlížeč
- voda MeSH
Novel star polymer-doxorubicin conjugates designed for passive tumor targeting have been developed and their potential for treatment of cancer has been investigated. In the present study the synthesis, physico-chemical characterization, drug release, bio-distribution and preliminary data of in vivo efficacy of the conjugates are described. In the water-soluble conjugates the core of a molecule formed by poly(amido amine) (PAMAM) dendrimers was grafted with semitelechelic N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers bearing doxorubicin (Dox) attached by hydrazone bonds enabling intracellular pH-controlled hydrolytic drug release, or by GFLG sequence susceptible to enzymatic degradation. The controlled synthesis utilizing semitelechelic copolymer precursors facilitated preparation of polymer conjugates in a broad range of molecular weights (1.1-3.0·10(5) g/mol). In contrast to free drug or linear conjugates the star polymer-Dox conjugates exhibited prolonged blood circulation and enhanced tumor accumulation in tumor-bearing mice indicating important role of the EPR effect. The star polymer-Dox conjugates showed significantly higher anti-tumor activity in vivo than Dox?HCl or its linear or graft polymer conjugates, if treated with a single dose 15 or 5 mg Dox eq./kg. Method of tumor initialization (acute or chronic experimental tumor models) significantly influenced effectiveness of the treatment with much lower success in treatment of mice bearing chronic tumors.
Citace poskytuje Crossref.org
Evaluation of linear versus star-like polymer anti-cancer nanomedicines in mouse models
Structure-to-Efficacy Relationship of HPMA-Based Nanomedicines: The Tumor Spheroid Penetration Study
