Translational studies of phenotypic probes for the mononuclear phagocyte system and liposomal pharmacology

J Pharmacol Exp Ther. 2013 Dec;347(3):599-606. doi: 10.1124/jpet.113.208801. Epub 2013 Sep 16.


As nanoparticles (NPs) are cleared via phagocytes of the mononuclear phagocyte system (MPS), we hypothesized that the function of circulating monocytes and dendritic cells (MO/DC) in blood can predict NP clearance (CL). We measured MO/DC phagocytosis and reactive oxygen species (ROS) production in mice, rats, dogs, and patients with refractory solid tumors. Pharmacokinetic studies of polyethylene glycol (PEG)-encapsulated liposomal doxorubicin (PEGylated liposomal doxirubicin [PLD]), CKD-602 (S-CKD602), and cisplatin (SPI-077) were performed at the maximum tolerated dose. MO/DC function was also evaluated in patients with recurrent epithelial ovarian cancer (EOC) administered PLD. Across species, a positive association was observed between cell function and CL of PEGylated liposomes. In patients with EOC, associations were observed between PLD CL and phagocytosis (R(2) = 0.43, P = 0.04) and ROS production (R(2) = 0.61, P = 0.008) in blood MO/DC. These findings suggest that probes of MPS function may help predict PEGylated liposome CL across species and PLD CL in patients with EOC.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use
  • Area Under Curve
  • Dendritic Cells / drug effects
  • Dogs
  • Drug Compounding
  • Female
  • Half-Life
  • Humans
  • Liposomes / pharmacology*
  • Mice
  • Middle Aged
  • Mononuclear Phagocyte System / drug effects*
  • Nanoparticles
  • Ovarian Neoplasms / drug therapy
  • Phagocytosis / drug effects
  • Pharmacokinetics
  • Phenotype
  • Polyethylene Glycols
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism
  • Translational Research, Biomedical


  • Antineoplastic Agents
  • Liposomes
  • Reactive Oxygen Species
  • Polyethylene Glycols