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

TitleTranslational studies of phenotypic probes for the mononuclear phagocyte system and liposomal pharmacology.
Publication TypeJournal Article
Year of Publication2013
AuthorsCaron, Whitney P., John C. Lay, Alan M. Fong, Ninh M. La-Beck, Parag Kumar, Suzanne E. Newman, Haibo Zhou, Jane H. Monaco, Daniel L. Clarke-Pearson, Wendy R. Brewster, Linda Van Le, Victoria L. Bae-Jump, Paola A. Gehrig, and William C. Zamboni
JournalJ Pharmacol Exp Ther
Volume347
Issue3
Pagination599-606
Date Published2013 Dec
ISSN1521-0103
KeywordsAdult, Aged, Animals, Antineoplastic Agents, Area Under Curve, Dendritic Cells, Dogs, Drug Compounding, Female, Half-Life, Humans, Liposomes, Mice, Middle Aged, Mononuclear Phagocyte System, Nanoparticles, Ovarian Neoplasms, Phagocytosis, Pharmacokinetics, Phenotype, Polyethylene Glycols, Rats, Rats, Sprague-Dawley, Reactive Oxygen Species, Translational Research, Biomedical
Abstract

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.

DOI10.1124/jpet.113.208801
Alternate JournalJ Pharmacol Exp Ther
Original PublicationTranslational studies of phenotypic probes for the mononuclear phagocyte system and liposomal pharmacology.
PubMed ID24042160
PubMed Central IDPMC3836305
Grant ListP30 CA016086 / CA / NCI NIH HHS / United States
P01-CA142538 / CA / NCI NIH HHS / United States
1U54-CA151652-01 / CA / NCI NIH HHS / United States
R01-ES0201900 / ES / NIEHS NIH HHS / United States
U54 CA151652 / CA / NCI NIH HHS / United States
P01 CA142538 / CA / NCI NIH HHS / United States
Project: