The comparison of in vivo properties of water-soluble HPMA-based polymer conjugates with doxorubicin prepared by controlled RAFT or free radical polymerization

Physiol Res. 2015;64(Suppl 1):S41-9. doi: 10.33549/physiolres.933137.


Two conjugates of anticancer drug doxorubicin (Dox) covalently bound by the hydrolytically degradable hydrazone bond to the polymer carrier based on water-soluble N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers were synthesized and their properties were compared, namely their behavior in vivo. The polymer carriers differed in dispersity due to different methods of synthesis; the carrier with relatively high dispersity (HD) was prepared by free radical polymerization (Mw=29,900 g/mol, D=1.75) and the carrier with low dispersity (LD) by controlled radical polymerization (Mw=30,000 g/mol, D=1.13). Both polymer-Dox conjugates showed prolonged blood circulation and tumor accumulation of the drug in comparison with the free drug; e.g. the tumor-to-blood ratio for the polymer-bound Dox was 3-5 times higher. The LD polymer-Dox conjugate exhibited moderately higher tumor accumulation than the HD one at a dose of 1x15 mg Dox (eq.)/kg. Also, their anti-tumor activity did not differ when injected at this dose. However, the increase of the dose to 1x25 mg Dox (eq.)/kg resulted in the enhanced therapeutic activity of the conjugates, especially of the LD one with 100% of long-term survivals. The dispersity of polymer drug carriers influenced the tumor accumulation rate, which affected the overall anti-cancer activity of polymer-drug conjugates.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / chemistry*
  • Antibiotics, Antineoplastic / pharmacokinetics
  • Antibiotics, Antineoplastic / pharmacology
  • Delayed-Action Preparations
  • Doxorubicin / chemistry*
  • Doxorubicin / pharmacokinetics
  • Doxorubicin / pharmacology
  • Drug Carriers
  • Female
  • Free Radicals / chemistry
  • Male
  • Methacrylates / chemistry*
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms, Experimental / drug therapy
  • Neoplasms, Experimental / metabolism
  • Neoplasms, Experimental / pathology
  • Polymers / chemical synthesis*
  • Survival Analysis
  • Tissue Distribution
  • Xenograft Model Antitumor Assays


  • Antibiotics, Antineoplastic
  • Delayed-Action Preparations
  • Drug Carriers
  • Free Radicals
  • Methacrylates
  • Polymers
  • Doxorubicin
  • hydroxypropyl methacrylate