Title | Translational studies of phenotypic probes for the mononuclear phagocyte system and liposomal pharmacology. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Caron, 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 |
Journal | J Pharmacol Exp Ther |
Volume | 347 |
Issue | 3 |
Pagination | 599-606 |
Date Published | 2013 Dec |
ISSN | 1521-0103 |
Keywords | Adult, 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. |
DOI | 10.1124/jpet.113.208801 |
Alternate Journal | J Pharmacol Exp Ther |
Original Publication | Translational studies of phenotypic probes for the mononuclear phagocyte system and liposomal pharmacology. |
PubMed ID | 24042160 |
PubMed Central ID | PMC3836305 |
Grant List | P30 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 |
Translational studies of phenotypic probes for the mononuclear phagocyte system and liposomal pharmacology.
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