Clinical implications of N-(2-hydroxypropyl)methacrylamide copolymers
Language English Country Netherlands Media print
Document type Journal Article, Research Support, Non-U.S. Gov't, Review
- MeSH
- Acrylamides administration & dosage chemistry MeSH
- Clinical Trials, Phase I as Topic MeSH
- Humans MeSH
- Molecular Structure MeSH
- Neoplasms drug therapy MeSH
- Drug Carriers administration & dosage chemistry MeSH
- Antineoplastic Agents administration & dosage chemistry therapeutic use MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- Acrylamides MeSH
- N-(2-hydroxypropyl)methacrylamide MeSH Browser
- Drug Carriers MeSH
- Antineoplastic Agents MeSH
Different anticancer drugs, farmorubicin, doxorubicin, paclitaxel and cis-platin have been conjugated through a Gly-Phe-Leu-Gly tetrapeptide side chain to a water-soluble synthetic polymeric carrier based on N-(2-hydroxypropyl)methacryalmide (HPMA) non-targeted or targeted with galactosamine and/or human IVIg and used in Phase I clinical trials. Conjugation of the drugs to the polymeric carrier that is non-toxic and non-immunogenic in man significantly decreased their non-specific organ toxicities and increased maximum tolerated dose up to 5 times. Macromolecular therapeutics based on HPMA have radically different pharmacokinetics. Drugs are not released from their polymeric carrier and remain in the peripheral blood and urine of patients mostly in their polymer-bound form. A clinical response against some refractory cancers was recorded in Phase I clinical trials. It was also demonstrated that doxorubicin-HPMA copolymer conjugates containing an immunoglobulin moiety have both cytostatic and immunomobilizing activity.
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