Polymer conjugates of doxorubicin bound through an amide and hydrazone bond: Impact of the carrier structure onto synergistic action in the treatment of solid tumours
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
24632485
DOI
10.1016/j.ejps.2014.02.016
PII: S0928-0987(14)00090-6
Knihovny.cz E-zdroje
- Klíčová slova
- Doxorubicin, Drug delivery, HPMA copolymer, In vivo efficacy, Synergistic effect,
- MeSH
- akrylamidy chemie MeSH
- doxorubicin chemie farmakokinetika farmakologie terapeutické užití MeSH
- hydrazony chemie MeSH
- koncentrace vodíkových iontů MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nádory farmakoterapie metabolismus MeSH
- nosiče léků chemie farmakologie MeSH
- protinádorová antibiotika chemie farmakokinetika farmakologie terapeutické užití MeSH
- stabilita léku MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- akrylamidy MeSH
- doxorubicin MeSH
- hydrazony MeSH
- N-(2-hydroxypropyl)methacrylamide MeSH Prohlížeč
- nosiče léků MeSH
- protinádorová antibiotika MeSH
In this study, we describe the synthesis, physico-chemical characterisation and results of the in vitro and in vivo evaluation of the biological behaviour of N-(2-hydroxypropyl)methacrylamide-based (HPMA) copolymer conjugates bearing doxorubicin (DOX) partly bound via a pH-sensitive hydrazone and partly via enzymatically degradable amide bonds, each contributing to a different anti-tumour mechanism of action of the polymer-doxorubicin conjugate. The following two types of HPMA copolymer drug carriers designed for passive tumour targeting were synthesised and compared: the linear non-degradable copolymer and the biodegradable high-molecular-weight (HMW) diblock copolymer. The HMW diblock copolymer carrier containing a degradable disulphide bond between the polymer blocks showed a rapid degradation in a buffer containing glutathione within the first few hours of incubation. In contrast to the conjugate with the amide bond-bound DOX requiring the presence of lysosomal enzymes to release DOX, the polymer-drug conjugate with the DOX bound via a hydrazone bond released DOX by pH-sensitive hydrolysis, which was significantly faster in a buffer of pH 5.0 (intracellular pH) than pH 7.4, mimicking the conditions in the bloodstream. The significant and comparable in vivo anti-tumour activity of the diblock HMW conjugate and an equimolar mixture of the conjugates differing in the DOX attachment method along with the development of cancer resistance during treatment with these conjugates demonstrated the high potential of these compounds in the development of new nanomedicines suitable for the treatment of solid tumours.
Citace poskytuje Crossref.org
HPMA Copolymer-Based Nanomedicines in Controlled Drug Delivery
