Novel star HPMA-based polymer conjugates for passive targeting to solid tumors
Language English Country Great Britain, England Media print-electronic
Document type Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Acrylamides chemistry MeSH
- Dendrimers chemistry MeSH
- Doxorubicin administration & dosage chemistry pharmacokinetics MeSH
- Hydrogen-Ion Concentration MeSH
- Drug Delivery Systems * MeSH
- Delayed-Action Preparations MeSH
- Lymphoma, T-Cell drug therapy pathology MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- Drug Carriers chemistry MeSH
- Antibiotics, Antineoplastic administration & dosage chemistry pharmacokinetics MeSH
- Solubility MeSH
- Tissue Distribution MeSH
- Water chemistry MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Names of Substances
- Acrylamides MeSH
- Dendrimers MeSH
- Doxorubicin MeSH
- Delayed-Action Preparations MeSH
- N-(2-hydroxypropyl)methacrylamide MeSH Browser
- Drug Carriers MeSH
- PAMAM Starburst MeSH Browser
- Antibiotics, Antineoplastic MeSH
- Water 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.
References provided by 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
