Comparison of Quantum Dot Biodistribution with a Blood-Flow-Limited Physiologically Based Pharmacokinetic Model

College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606, USA.
Nano Letters (Impact Factor: 13.59). 02/2009; 9(2):794-9. DOI: 10.1021/nl803481q
Source: PubMed


A physiologically based pharmacokinetic model with partition coefficients estimated from quantum dot (QD) 705 biodistribution was compared with the biodistribution of other QDs in mice and rats to determine the model's predictive ability across QD types, species, and exposure routes. The model predicted the experimentally observed persistence of QDs in tissues but not early time profiles or different QD biodistribution. Therefore, more complex models will be needed to better predict QD biodistribution in vivo.

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Available from: Nancy A Monteiro-Riviere
    • "PBPK models have been commonly developed for drugs to help in the design of therapeutic regimens (Jones et al., 2013; Lin et al., 2015), to aid predictive risk assessment for environmental toxicants (Andersen et al., 1987; Fisher et al., 2011; Lin et al., 2013), as well as to predict drug withdrawal time in food-producing animals (Buur et al., 2008; Leavens et al., 2014). In the field of nanomedicine, researchers have begun to employ PBPK models to simulate the pharmacokinetics of NPs, including quantum dots (Lee et al., 2009; Lin et al., 2008), carbon (Pery et al., 2009), silver (Bachler et al., 2013; Lankveld et al., 2010), titanium dioxide (Bachler et al., 2014), polyacrylamide (Li et al., 2014), poly(lactic-co-glycolic) acid (Li et al., 2012) NPs, and gold/dendrimer composite nanodevices (Mager et al., 2012). These models greatly improve our understanding of the pharmacokinetics of NPs; some of these models have been extrapolated to humans and proved to be helpful in risk assessment (Bachler et al., 2013, 2014). "
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    ABSTRACT: Nanoparticles (NPs) are widely used in various fields of nanomedicine. A systematic understanding of NP pharmacokinetics is crucial in their design, applications, and risk assessment. In order to integrate available experimental information and to gain insights into NP pharmacokinetics, a membrane-limited physiologically based pharmacokinetic (PBPK) model for polyethylene glycol-coated gold (Au) NPs (PEG-coated AuNPs) was developed in mice. The model described endocytosis of the NPs in the liver, spleen, kidneys, and lungs and was calibrated using data from mice that were intravenously injected with 0.85 mg/kg 13 nm and 100 nm PEG-coated AuNPs. The model adequately predicted multiple external datasets for PEG-coated AuNPs of similar sizes (13-20 nm; 80-100 nm), indicating reliable predictive capability in suitable size ranges. Simulation results suggest that endocytosis of NPs is time and size dependent, i.e. endocytosis of larger NPs occurs immediately and predominately from the blood, whereas smaller NPs can diffuse through the capillary wall and their endocytosis appears mainly from the tissue with a 10-h delay, which may be the primary mechanism responsible for the reported size-dependent pharmacokinetics of NPs. Several physiological parameters (e.g. liver weight fraction of body weight) were identified to have a high influence on selected key dose metrics, indicating the need for additional interspecies comparison and scaling studies and to conduct pharmacokinetic studies of NPs in species that are more closely related to humans in these parameters. This PBPK model provides useful insights into the size, time, and species dependence of NP pharmacokinetics.
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    • "One of the issues in the development of the models is the need to accurately describe the distribution of the nanoparticles in the tissues, as the blood-flow limited model most commonly used for chemicals (International Programme on Chemical Safety, 2010) will not be appropriate for nanoparticles [5] [6]. Although intraventricular delivery of drugs to the CSF is known to result in greater drug concentration with a longer halflife in the CSF, drug penetration in the parenchyma is limited, with most of the drug being taken up by the ependymal cells lining the ventricles rather than the target cells [7] [8]. "
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    • "Since the early 1990s, PBPK models had been developed for five potentially toxic metals: arsenic, chromium, lead, nickel, and zinc.23 More recently, PBPK models for NPs have been published for carbon,24 poly(lactic-co-glycolic) acid (PLGA),25 silver,26 and quantum dots.27 However, with the exception of the model for PLGA NPs, no PBPK model could successfully be validated against independent data. "
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