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Research ArticleChemotherapy, Antibiotics, and Gene Therapy

Translational Studies of Phenotypic Probes for the Mononuclear Phagocyte System and Liposomal Pharmacology

Whitney P. Caron, 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 of Pharmacology and Experimental Therapeutics September 16, 2013, jpet.113.208801; DOI: https://doi.org/10.1124/jpet.113.208801
Whitney P. Caron
1 University of North Carolina at Chapel Hill;
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John C. Lay
1 University of North Carolina at Chapel Hill;
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Alan M. Fong
1 University of North Carolina at Chapel Hill;
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Ninh M. La-Beck
2 Texas Tech University Health Sciences Center
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Parag Kumar
1 University of North Carolina at Chapel Hill;
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Suzanne E. Newman
1 University of North Carolina at Chapel Hill;
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Haibo Zhou
1 University of North Carolina at Chapel Hill;
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Jane H. Monaco
1 University of North Carolina at Chapel Hill;
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Daniel L. Clarke-Pearson
1 University of North Carolina at Chapel Hill;
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Wendy R. Brewster
1 University of North Carolina at Chapel Hill;
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Linda Van Le
1 University of North Carolina at Chapel Hill;
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Victoria L. Bae-Jump
1 University of North Carolina at Chapel Hill;
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Paola A. Gehrig
1 University of North Carolina at Chapel Hill;
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William C. Zamboni
1 University of North Carolina at Chapel Hill;
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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.

  • cancer chemotherapy
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  • immunopharmacology
  • pharmacodynamics
  • pharmacokinetics
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Journal of Pharmacology and Experimental Therapeutics: 384 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 384, Issue 2
1 Feb 2023
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Research ArticleChemotherapy, Antibiotics, and Gene Therapy

Translational Studies of Phenotypic Probes for the Mononuclear Phagocyte System and Liposomal Pharmacology

Whitney P. Caron, 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 of Pharmacology and Experimental Therapeutics September 16, 2013, jpet.113.208801; DOI: https://doi.org/10.1124/jpet.113.208801

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Research ArticleChemotherapy, Antibiotics, and Gene Therapy

Translational Studies of Phenotypic Probes for the Mononuclear Phagocyte System and Liposomal Pharmacology

Whitney P. Caron, 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 of Pharmacology and Experimental Therapeutics September 16, 2013, jpet.113.208801; DOI: https://doi.org/10.1124/jpet.113.208801
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