Abstract
Purpose: As nanoparticles (NP) 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). Methods: MO/DC phagocytosis and reactive oxygen species (ROS) production were measured in mice, rats, dogs, and patients with refractory solid tumors. PK studies of PEGylated liposomal doxorubicin (PLD), CKD-602 (S-CKD602), and cisplatin (SPI-077) were performed at the MTD. MO/DC function was also evaluated in patients with recurrent epithelial ovarian cancer (EOC) administered PLD. Results: 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 [R2 = 0.43, P= 0.04] and ROS production [R2 = 0.61, P= 0.008] in blood MO/DC. Conclusions: These findings suggest that probes of MPS function may help predict PEGylated liposome CL across species and PLD CL in patients with EOC.
- The American Society for Pharmacology and Experimental Therapeutics