| Literature DB >> 24042160 |
Whitney P Caron1, 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, William C Zamboni.
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.Entities:
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Year: 2013 PMID： 24042160 PMCID： PMC3836305 DOI： 10.1124/jpet.113.208801
Source DB: PubMed Journal: J Pharmacol Exp Ther ISSN： 0022-3565 Impact factor: 4.030