Evaluation of PolyMPC-Dox Prodrugs in a Human Ovarian Tumor Model

Mol Pharm. 2016 May 2;13(5):1679-87. doi: 10.1021/acs.molpharmaceut.6b00092. Epub 2016 Mar 29.


A polymer prodrug, composed of doxorubicin (Dox) conjugated covalently to poly(methacryloyloxyethyl phosphorylcholine) (polyMPC), was evaluated for the treatment of human ovarian tumors in animals. PolyMPC-Dox prodrugs were prepared using facile conjugation chemistry to yield conjugates soluble in water and injectable saline, with a Dox loading of ∼19 weight percent. Toxicity evaluation showed that polyMPC was well-tolerated in mice at doses up to 800 mg/kg, confirming the biocompatibility of the polymer carrier at a high concentration. Additionally, the polyMPC-Dox prodrug was well-tolerated in animals at a Dox equivalent dose of 10 mg/kg, greater than twice the maximum tolerated dose of free Dox (∼4 mg/kg) in the same mouse strain. In a human ovarian tumor model (SKOV-3), polyMPC-Dox accumulated in tumors at twice the level of free Dox, with no additional off-target organ uptake, a result of improved pharmacokinetics afforded by the prodrug and passive targeting attributed to an enhanced permeability and retention effect. When administered to human ovarian tumor-bearing mice using a recurring dosing regimen comparable to that used clinically, polyMPC-Dox significantly retarded tumor growth relative to treatment with free Dox. Moreover, animals treated with multiple doses of polyMPC-Dox (eight total doses) exhibited enhanced survival, with a notably reduced incidence of toxicity or adverse events relative to mice treated with free Dox. These in vivo results demonstrate advantages of treating human ovarian tumors with polyMPC-Dox, including reduced systemic toxicity, improved drug accumulation in tumors, and enhanced therapeutic efficacy.

Keywords: doxorubicin; drug delivery; ovarian cancer; poly(methacryloyloxyethyl phosphorylcholine); polymer prodrug.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Cell Line, Tumor
  • Doxorubicin / administration & dosage*
  • Doxorubicin / chemistry*
  • Female
  • Humans
  • Maximum Tolerated Dose
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Ovarian Neoplasms / drug therapy*
  • Phosphorylcholine / chemistry*
  • Polymers / chemistry*
  • Prodrugs / administration & dosage*
  • Prodrugs / chemistry*


  • Antineoplastic Agents
  • Polymers
  • Prodrugs
  • Phosphorylcholine
  • Doxorubicin