New HPMA copolymer-based drug carriers with covalently bound hydrophobic substituents for solid tumour targeting
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
18304673
DOI
10.1016/j.jconrel.2008.01.007
PII: S0168-3659(08)00061-8
Knihovny.cz E-resources
- MeSH
- Doxorubicin analogs & derivatives chemistry pharmacokinetics pharmacology MeSH
- Hydrophobic and Hydrophilic Interactions MeSH
- Polymethacrylic Acids chemistry pharmacokinetics pharmacology MeSH
- Humans MeSH
- Methacrylates chemistry pharmacokinetics pharmacology MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- Cell Line, Tumor MeSH
- Neoplasms drug therapy metabolism MeSH
- Drug Carriers chemistry pharmacokinetics pharmacology MeSH
- Cell Proliferation drug effects MeSH
- Antibiotics, Antineoplastic chemistry pharmacokinetics pharmacology MeSH
- Neoplasm Transplantation MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- doxorubicin-N-(2-hydroxypropyl)methacrylamide copolymer conjugate MeSH Browser
- Doxorubicin MeSH
- hydroxypropyl methacrylate MeSH Browser
- Polymethacrylic Acids MeSH
- Methacrylates MeSH
- Drug Carriers MeSH
- Antibiotics, Antineoplastic MeSH
Various conjugates of anticancer drug doxorubicin (Dox) covalently bound by the hydrolytically degradable hydrazone bond to the drug carrier based on N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers were synthesised. Structure of the conjugates differed in the type and the content of hydrophobic substituent (dodecyl, oleic acid and cholesterol moieties) introduced into the polymer structure. In aqueous solutions the conjugates self-assembled into high-molecular-weight supramolecular structures, such as polymeric micelles or stable hydrophilic nanoparticles 13-37 nm in diameter, depending on the type and the content of hydrophobic substituents. Treatment of mice bearing EL-4 T cell lymphoma with the conjugates in the therapeutic regime of drug administration (i.v.) resulted in significant tumour regression with up to 100% of long-term survivors, depending on the dose and the detailed structure of the carrier. The nanoparticles formed by the conjugate bearing cholesterol moiety exhibited prolonged blood circulation and enhanced tumour accumulation indicating an important role of the EPR effect in excellent anticancer activity of the conjugate.
References provided by Crossref.org
Octahedral Molybdenum Cluster-Based Nanomaterials for Potential Photodynamic Therapy
HPMA Copolymer-Based Nanomedicines in Controlled Drug Delivery
