title: Physiologically Based Pharmacokinetic Modeling of Fluorescently Labeled Block Copolymer Nanoparticles for Controlled Drug Delivery in Leukemia Therapy.
abstract: A physiologically based pharmacokinetic (PBPK) model was developed that describes the concentration and biodistribution of fluorescently labeled nanoparticles in mice used for the controlled delivery of dexamethasone in acute lymphoblastic leukemia (ALL) therapy. The simulated data showed initial spikes in nanoparticle concentration in the liver, spleen, and kidneys, whereas concentration in plasma decreased rapidly. These simulation results were consistent with previously published in vivo data. At shorter time scales, the simulated data predicted decrease of nanoparticles from plasma with concomitant increase in the liver, spleen, and kidneys before decaying at longer timepoints. Interestingly, the simulated data predicted an unaccounted accumulation of about 50% of the injected dose of nanoparticles. Incorporation of an additional compartment into the model justified the presence of unaccounted nanoparticles in this compartment. Our results suggest that the proposed PBPK model can be an excellent tool for prediction of optimal dose of nanoparticle-encapsulated drugs for cancer treatment.
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Delaware Newark, Delaware, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Gilkey
authors.affiliation: Department of Materials Science and Engineering, University of Delaware Newark, Delaware, USA ; Nemours Biomedical Research, A I DuPont Hospital for Children Wilmington, Delaware, USA.
authors.forename: V
authors.initials: V
authors.lastname: Krishnan
authors.affiliation: Department of Biomedical Engineering, University of Delaware Newark, Delaware, USA.
authors.forename: L
authors.initials: L
authors.lastname: Scheetz
authors.affiliation: Department of Materials Science and Engineering, University of Delaware Newark, Delaware, USA ; Department of Biomedical Engineering, University of Delaware Newark, Delaware, USA ; Department of Biological Sciences, Center for Translational Cancer Research, University of Delaware Newark, Delaware, USA.
authors.forename: X
authors.initials: X
authors.lastname: Jia
authors.affiliation: Department of Materials Science and Engineering, University of Delaware Newark, Delaware, USA ; Department of Biological Sciences, Center for Translational Cancer Research, University of Delaware Newark, Delaware, USA ; Lankenau Institute for Medical Research Wynnewood, Pennsylvania, USA.
authors.forename: A K
authors.initials: AK
authors.lastname: Rajasekaran
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Delaware Newark, Delaware, USA.
authors.forename: P S
authors.initials: PS
authors.lastname: Dhurjati