N-(2-Hydroxypropyl)methacrylamide-based polymer conjugates with pH-controlled activation of doxorubicin for cell-specific or passive tumour targeting. Synthesis by RAFT polymerisation and physicochemical characterisation
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
20696244
DOI
10.1016/j.ejps.2010.08.003
PII: S0928-0987(10)00285-X
Knihovny.cz E-zdroje
- MeSH
- akrylamidy chemie MeSH
- doxorubicin chemie farmakologie MeSH
- kinetika MeSH
- koncentrace vodíkových iontů MeSH
- lékové transportní systémy metody MeSH
- molekulární struktura MeSH
- monoklonální protilátky MeSH
- nosiče léků chemie MeSH
- polymerizace MeSH
- protinádorová antibiotika chemie farmakologie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- akrylamidy MeSH
- doxorubicin MeSH
- monoklonální protilátky MeSH
- N-(2-hydroxypropyl)methacrylamide MeSH Prohlížeč
- nosiče léků MeSH
- protinádorová antibiotika MeSH
Controlled radical reversible addition-fragmentation chain transfer (RAFT) polymerisation was used to prepare water-soluble polymer-drug carriers based on copolymers of N-(2-hydroxypropyl)methacrylamide (HPMA) with a hydrazide group-containing monomer, showing well-defined structure with narrow molecular weight distribution (approx. 1.1-1.2). The anticancer therapeutic doxorubicin was bound to the polymeric carrier by a hydrazone bond, enabling pH-controlled release under mildly acid conditions that mimics the environment in endosomes/lysosomes of tumour cells. RAFT polymerisation facilitated the synthesis of semitelechelic copolymers, which were used in the synthesis of monoclonal anti-CD20 antibody-polymer-drug conjugate designed for cell-specific tumour targeting. They were also used for producing a biodegradable high-molecular-weight graft polymer-drug conjugate that degrade in the presence of glutathione, which is designed for passive targeting to solid tumours. The conjugates exhibited well-defined structures with narrow molecular weight distributions of approx. 1.3 and pH-controlled drug release.
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