Polymeric anticancer drugs with pH-controlled activation

• Published in: International journal of pharmaceutics 2004-06, Vol.277 (1), p.63-72
• Main Authors: Ulbrich, K, Etrych, T, Chytil, P, Pechar, M, Jelinkova, M, Rihova, B
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacokinetics; Antitumor activity; Biological and medical sciences; Cell Line, Tumor; Cytotoxicity; Doxorubicin; Doxorubicin - administration & dosage; Doxorubicin - analogs & derivatives; Doxorubicin - pharmacokinetics; Drug targeting; General pharmacology; HPMA copolymers; Humans; Hydrogen-Ion Concentration; Lymphoma, T-Cell - drug therapy; Lymphoma, T-Cell - metabolism; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Neoplasms - drug therapy; Neoplasms - metabolism; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Poly(ethylene glycol); Polymers - administration & dosage; Polymers - pharmacokinetics; Polymethacrylic Acids - administration & dosage; Polymethacrylic Acids - pharmacokinetics; Xenograft Model Antitumor Assays - methods
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2003.02.001

The paper is dealing with the synthesis and properties of new, nontargeted or antibody-targeted pH-sensitive polymer–doxorubicin (DOX) conjugates designed as anticancer drugs facilitating site-specific therapy. These conjugates are stable and inactive during transport in the body but activate inside target cells as a result of pH changes outside and inside the cells. Cytotoxicity of the conjugates depends on the detailed structure of the polymer and of the spacer between the drug and polymer carrier. In both protective and therapeutic regimes of drug administration, the in vivo antitumor activity of the pH-sensitive conjugates containing DOX was significantly enhanced (T-cell lymphoma EL 4, C57BL/16 mice) in comparison with the free DOX or classic PK1, the PHPMA–DOX conjugate clinically tested at present.