A physiologically based pharmacokinetic model to predict the superparamagnetic iron oxide nanoparticles (SPIONs) accumulation in vivo

Authors
Henrique Silva, Adny; Lima, Enio Junior; Vasquez Mansilla, Marcelo; Zysler, Roberto Daniel; Mojica Pisciotti, Mary Luz; Locatelli, Claudriana; Kumar Reddy Rajoli, Rajith; Owen, Andrew; Creczynski Pasa, Tânia Beatriz; Siccardi, Marco
Publication Year
2017
Language
English
Format
article
Status
Published version
Description
Superparamagnetic iron oxide nanoparticles (SPIONs) have been identified as a promising material for biomedical applications. These include as contrast agents for medical imaging, drug delivery and/or cancer cell treatment. The nanotoxicological profile of SPIONs has been investigated in different studies and the distribution of SPIONs in the human body has not been fully characterized. The aim of this study was to develop a physiologically-based pharmacokinetic (PBPK) model to predict the pharmacokinetics of SPIONs. The distribution and accumulation of SPIONs in organs were simulated taking into consideration their penetration through capillary walls and their active uptake by specialized macrophages in the liver, spleen and lungs. To estimate the kinetics of SPION uptake, a novel experimental approach using primary macrophages was developed. The murine PBPK model was validated against in vivo pharmacokinetic data, and accurately described accumulation in liver, spleen and lungs. After validation of the murine model, a similar PBPK approach was developed to simulate the distribution of SPIONs in humans. These data demonstrate the utility of PBPK modeling for estimating biodistribution of inorganic nanoparticles and represents an initial platform to provide computational prediction of nanoparticle pharmacokinetics.
Fil: Henrique Silva, Adny. Universidade Federal de Santa Catarina; Brasil
Fil: Lima, Enio Junior. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina
Fil: Vasquez Mansilla, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina
Fil: Zysler, Roberto Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina
Fil: Mojica Pisciotti, Mary Luz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina
Fil: Locatelli, Claudriana. Universidade do Alto Vale do Rio do Peixe; Brasil. Universidade do Oeste de Santa Catarina; Brasil
Fil: Kumar Reddy Rajoli, Rajith. University of Liverpool; Reino Unido
Fil: Owen, Andrew. University of Liverpool; Reino Unido
Fil: Creczynski Pasa, Tânia Beatriz. Universidade Federal de Santa Catarina; Brasil
Fil: Siccardi, Marco. University of Liverpool; Reino Unido
Subject
ACCUMULATION
BIODISTRIBUTION
NANOPARTICLES
PHYSIOLOGICALLY BASED PHARMACOKINETIC MODEL
PREDICTION
Nano-materiales
Nanotecnología
INGENIERÍAS Y TECNOLOGÍAS
Otras Ciencias Biológicas
Ciencias Biológicas
CIENCIAS NATURALES Y EXACTAS
Access level
Open access
License
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repository
CONICET Digital (CONICET)
Institution
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identifier
oai:ri.conicet.gov.ar:11336/57895