Conjugates of doxorubicin with graft HPMA copolymers for passive tumor targeting
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
18534705
DOI
10.1016/j.jconrel.2008.04.017
PII: S0168-3659(08)00222-8
Knihovny.cz E-resources
- MeSH
- Acrylamides administration & dosage chemical synthesis pharmacokinetics pharmacology MeSH
- Antibiotics, Antineoplastic administration & dosage chemical synthesis pharmacokinetics pharmacology MeSH
- Biological Transport MeSH
- Cell Line MeSH
- Chemistry, Pharmaceutical MeSH
- Doxorubicin administration & dosage chemical synthesis pharmacokinetics pharmacology MeSH
- Hydrolysis MeSH
- Injections, Intravenous MeSH
- Hydrogen-Ion Concentration MeSH
- Delayed-Action Preparations MeSH
- Lymphoma drug therapy metabolism pathology MeSH
- Molecular Weight MeSH
- Mice, Inbred C3H MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- Drug Carriers * MeSH
- Xenograft Model Antitumor Assays MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Acrylamides MeSH
- Antibiotics, Antineoplastic MeSH
- Doxorubicin MeSH
- Delayed-Action Preparations MeSH
- N-(2-hydroxypropyl)methacrylamide co-polymer-doxorubicin conjugate MeSH Browser
- Drug Carriers * MeSH
Synthesis, physicochemical behavior, tumor accumulation and preliminary anticancer activity of a new biodegradable graft copolymer-doxorubicin (DOX) conjugates designed for passive tumor targeting were investigated. In the graft high-molecular-weight conjugates the multivalent N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer was grafted with a similar but semitelechelic HPMA copolymer; both types of polymer chains were bearing doxorubicin attached by hydrazone bonds enabling intracellular pH-controlled drug release. The polymer grafts were attached to the main chain through spacers, degradable enzymatically or reductively, facilitating, after the drug release, intracellular degradation of the graft polymer carrier to short fragments excretable from the organism by glomerular filtration. The graft polymer-DOX conjugate exhibited prolonged blood circulation and enhanced tumor accumulation in tumor-bearing mice indicating the important role of the EPR effect in the anticancer activity. The graft polymer-DOX conjugates showed a significantly higher antitumor activity in vivo than DOX.HCl or the linear polymer conjugate when tested in mice bearing 38C13 B-cell or EL4 T-cell lymphoma, with a significant number of long-term-surviving (LTS) mice with EL4 T-cell lymphoma treated with a single dose 15 mg DOX equiv./kg on day 10.
References provided by Crossref.org
HPMA Copolymer-Based Nanomedicines in Controlled Drug Delivery
