Physiologically based pharmacokinetic modeling of intravenously administered nanoformulated substances

Minnema, Jordi, Borgos, Sven Even F, Liptrott, Neill ORCID: 0000-0002-5980-8966, Vandebriel, Rob and Delmaar, Christiaan (2022) Physiologically based pharmacokinetic modeling of intravenously administered nanoformulated substances. DRUG DELIVERY AND TRANSLATIONAL RESEARCH, 12 (9). pp. 2132-2144.

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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.

Item Type:	Article
Uncontrolled Keywords:	Physiologically based pharmacokinetic modeling, Nanobiomaterials (NBMs), Biodistribution, Bayesian parameter estimation
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	13 May 2022 08:21
Last Modified:	18 Jan 2023 21:03
DOI:	10.1007/s13346-022-01159-w
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3154717