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Research Papers

Nanoparticle Mass Transfer From Lung Airways to Systemic Regions—Part II: Multi-Compartmental Modeling

[+] Author and Article Information
Arun V. Kolanjiyil

Department of Mechanical &
Aerospace Engineering,
North Carolina State University,
Raleigh, NC 27695

Clement Kleinstreuer

Department of Mechanical and
Aerospace Engineering,
North Carolina State University,
Raleigh, NC 27695;
Joint UNC-NCSU Department of
Biomedical Engineering,
North Carolina State University,
Raleigh, NC 27695
email: ck@ncsu.edu

1Corresponding author.

Contributed by the Bioengineering Division of ASME for publication in the Journal of Biomechanical Engineering. Manuscript received April 5, 2013; final manuscript received August 8, 2013; accepted manuscript posted September 6, 2013; published online October 9, 2013. Assoc. Editor: Naomi Chesler.

J Biomech Eng 135(12), 121004 (Oct 09, 2013) (12 pages) Paper No: BIO-13-1175; doi: 10.1115/1.4025333 History: Received April 05, 2013; Revised August 08, 2013; Accepted September 06, 2013

This is the second article of a two-part paper, combining high-resolution computer simulation results of inhaled nanoparticle deposition in a human airway model (Kolanjiyil and Kleinstreuer, 2013, “Nanoparticle Mass Transfer From Lung Airways to Systemic Regions—Part I: Whole-Lung Aerosol Dynamics,” ASME J. Biomech. Eng., 135(12), p. 121003) with a new multicompartmental model for insoluble nanoparticle barrier mass transfer into systemic regions. Specifically, it allows for the prediction of temporal nanoparticle accumulation in the blood and lymphatic systems and in organs. The multicompartmental model parameters were determined from experimental retention and clearance data in rat lungs and then the validated model was applied to humans based on pharmacokinetic cross-species extrapolation. This hybrid simulator is a computationally efficient tool to predict the nanoparticle kinetics in the human body. The study provides critical insight into nanomaterial deposition and distribution from the lungs to systemic regions. The quantitative results are useful in diverse fields such as toxicology for exposure-risk analysis of ubiquitous nanomaterial and pharmacology for nanodrug development and targeting.

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Figures

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Fig. 1

Nanoparticle translocations from lung epithelium to regional lymph nodes, blood circulation, and secondary organs

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Fig. 2

(a) Pictorial representation of the regional differentiation of a lung, and (b) multicompartment model structure describing the bio-kinetics of inhaled nanoparticles

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Fig. 3

Comparison of multicompartment model results, using optimized parameters, with experimental results: (a) normalized amounts of ultrafine particle retained in the lung, and (b) normalized amount of ultra-fine particle excreted from the lung

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Fig. 4

Comparison of amount of nanoparticle translocated to the olfactory bulb, calculated using the model with optimized parameter values for the complete lung, with experimental results

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Fig. 5

Comparison of normalized retention profiles predicted by the multicompartment model with the experimental results of Takenaka et al. [16] after using a multiplication factor of 0.25

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Fig. 6

Particle retention curves of rats and man as measured by Bailey et al. [43] and the retention curve extrapolated from the average values of HMT-rat, F344-rat, and SD-rat to human for: (a) 1.7μm particles, and (b) 0.8μm particles

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Fig. 7

Particle retention curves of rat and man as measured by Kreyling et al. [44] and the retention curve extrapolated from rat to human

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Fig. 8

Human lung retention fraction extrapolated from the rat lung retention fraction of Semmler et al. [13]

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Fig. 9

Model simulation for the NP inhalation in a human: (a) NP retention fraction for 800 days, (b) NP retention fraction followed for 2 days after inhalation, (c) amount of NPs translocated to the blood circulation system, (d) amount (cumulative) of NPs translocated to other organs from the blood circulation system, (e) amount (cumulative) of NPs translocated to the lymphatic system, and (f) amount (cumulative) of NPs translocated to the olfactory lobe in brain

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Fig. 10

Amount (cumulative) of ultrafine particles translocated to secondary organs through the blood circulation system

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