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Physiologically based pharmacokinetic modeling of intravenously administered nanoformulated substances

Abstract

The use of nanobiomaterials (NBMs) is becoming increasingly popular in the field of medicine. To improve the understanding on the biodistribution of NBMs, the present study aimed to implement and parametrize a physiologically based pharmacokinetic (PBPK) model. This model was used to describe the biodistribution of two NBMs after intravenous administration in rats, namely, poly(alkyl cyanoacrylate) (PACA) loaded with cabazitaxel (PACA-Cbz), and LipImage™ 815. A Bayesian parameter estimation approach was applied to parametrize the PBPK model using the biodistribution data. Parametrization was performed for two distinct dose groups of PACA-Cbz. Furthermore, parametrizations were performed three distinct dose groups of LipImage™ 815, resulting in a total of five different parametrizations. The results of this study indicate that the PBPK model can be adequately parametrized using biodistribution data. The PBPK parameters estimated for PACA-Cbz, specifically the vascular permeability, the partition coefficient, and the renal clearance rate, substantially differed from those of LipImage™ 815. This emphasizes the presence of kinetic differences between the different formulations and substances and the need of tailoring the parametrization of PBPK models to the NBMs of interest. The kinetic parameters estimated in this study may help to establish a foundation for a more comprehensive database on NBM-specific kinetic information, which is a first, necessary step towards predictive biodistribution modeling. This effort should be supported by the development of robust in vitro methods to quantify kinetic parameters.
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Category

Academic article

Language

English

Author(s)

  • Jordi Minnema
  • Sven Even Borgos
  • Neill Liptrott
  • Rob J. Vandebriel
  • Christiaan Delmaar

Affiliation

  • SINTEF Industry / Biotechnology and Nanomedicine
  • National Institute for Public Health and the Environment
  • University of Liverpool

Year

2022

Published in

Drug Delivery and Translational Research

ISSN

2190-393X

Volume

12

Page(s)

2132 - 2144

View this publication at Norwegian Research Information Repository