Cargando…

Physiologically Based Pharmacokinetic (PBPK) Model of Gold Nanoparticle-Based Drug Delivery System for Stavudine Biodistribution

Computational modelling has gained attention for evaluating nanoparticle-based drug delivery systems. Physiologically based pharmacokinetic (PBPK) modelling provides a mechanistic approach for evaluating drug biodistribution. The aim of this work is to develop a specific PBPK model to simulate stavu...

Descripción completa

Detalles Bibliográficos
Autores principales: Zazo, Hinojal, Colino, Clara I., Gutiérrez-Millán, Carmen, Cordero, Andres A., Bartneck, Matthias, Lanao, José M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8875329/
https://www.ncbi.nlm.nih.gov/pubmed/35214138
http://dx.doi.org/10.3390/pharmaceutics14020406
_version_ 1784657887088345088
author Zazo, Hinojal
Colino, Clara I.
Gutiérrez-Millán, Carmen
Cordero, Andres A.
Bartneck, Matthias
Lanao, José M.
author_facet Zazo, Hinojal
Colino, Clara I.
Gutiérrez-Millán, Carmen
Cordero, Andres A.
Bartneck, Matthias
Lanao, José M.
author_sort Zazo, Hinojal
collection PubMed
description Computational modelling has gained attention for evaluating nanoparticle-based drug delivery systems. Physiologically based pharmacokinetic (PBPK) modelling provides a mechanistic approach for evaluating drug biodistribution. The aim of this work is to develop a specific PBPK model to simulate stavudine biodistribution after the administration of a 40 nm gold nanoparticle-based drug delivery system in rats. The model parameters used have been obtained from literature, in vitro and in vivo studies, and computer optimization. Based on these, the PBPK model was built, and the compartments included were considered as permeability rate-limited tissues. In comparison with stavudine solution, a higher biodistribution of stavudine into HIV reservoirs and the modification of pharmacokinetic parameters such as the mean residence time (MRT) have been observed. These changes are particularly noteworthy in the liver, which presents a higher partition coefficient (from 0.27 to 0.55) and higher MRT (from 1.28 to 5.67 h). Simulated stavudine concentrations successfully describe these changes in the in vivo study results. The average fold error of predicted concentrations after the administration of stavudine-gold nanoparticles was within the 0.5–2-fold error in all of the tissues. Thus, this PBPK model approach may help with the pre-clinical extrapolation to other administration routes or the species of stavudine gold nanoparticles.
format Online
Article
Text
id pubmed-8875329
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-88753292022-02-26 Physiologically Based Pharmacokinetic (PBPK) Model of Gold Nanoparticle-Based Drug Delivery System for Stavudine Biodistribution Zazo, Hinojal Colino, Clara I. Gutiérrez-Millán, Carmen Cordero, Andres A. Bartneck, Matthias Lanao, José M. Pharmaceutics Article Computational modelling has gained attention for evaluating nanoparticle-based drug delivery systems. Physiologically based pharmacokinetic (PBPK) modelling provides a mechanistic approach for evaluating drug biodistribution. The aim of this work is to develop a specific PBPK model to simulate stavudine biodistribution after the administration of a 40 nm gold nanoparticle-based drug delivery system in rats. The model parameters used have been obtained from literature, in vitro and in vivo studies, and computer optimization. Based on these, the PBPK model was built, and the compartments included were considered as permeability rate-limited tissues. In comparison with stavudine solution, a higher biodistribution of stavudine into HIV reservoirs and the modification of pharmacokinetic parameters such as the mean residence time (MRT) have been observed. These changes are particularly noteworthy in the liver, which presents a higher partition coefficient (from 0.27 to 0.55) and higher MRT (from 1.28 to 5.67 h). Simulated stavudine concentrations successfully describe these changes in the in vivo study results. The average fold error of predicted concentrations after the administration of stavudine-gold nanoparticles was within the 0.5–2-fold error in all of the tissues. Thus, this PBPK model approach may help with the pre-clinical extrapolation to other administration routes or the species of stavudine gold nanoparticles. MDPI 2022-02-13 /pmc/articles/PMC8875329/ /pubmed/35214138 http://dx.doi.org/10.3390/pharmaceutics14020406 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zazo, Hinojal
Colino, Clara I.
Gutiérrez-Millán, Carmen
Cordero, Andres A.
Bartneck, Matthias
Lanao, José M.
Physiologically Based Pharmacokinetic (PBPK) Model of Gold Nanoparticle-Based Drug Delivery System for Stavudine Biodistribution
title Physiologically Based Pharmacokinetic (PBPK) Model of Gold Nanoparticle-Based Drug Delivery System for Stavudine Biodistribution
title_full Physiologically Based Pharmacokinetic (PBPK) Model of Gold Nanoparticle-Based Drug Delivery System for Stavudine Biodistribution
title_fullStr Physiologically Based Pharmacokinetic (PBPK) Model of Gold Nanoparticle-Based Drug Delivery System for Stavudine Biodistribution
title_full_unstemmed Physiologically Based Pharmacokinetic (PBPK) Model of Gold Nanoparticle-Based Drug Delivery System for Stavudine Biodistribution
title_short Physiologically Based Pharmacokinetic (PBPK) Model of Gold Nanoparticle-Based Drug Delivery System for Stavudine Biodistribution
title_sort physiologically based pharmacokinetic (pbpk) model of gold nanoparticle-based drug delivery system for stavudine biodistribution
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8875329/
https://www.ncbi.nlm.nih.gov/pubmed/35214138
http://dx.doi.org/10.3390/pharmaceutics14020406
work_keys_str_mv AT zazohinojal physiologicallybasedpharmacokineticpbpkmodelofgoldnanoparticlebaseddrugdeliverysystemforstavudinebiodistribution
AT colinoclarai physiologicallybasedpharmacokineticpbpkmodelofgoldnanoparticlebaseddrugdeliverysystemforstavudinebiodistribution
AT gutierrezmillancarmen physiologicallybasedpharmacokineticpbpkmodelofgoldnanoparticlebaseddrugdeliverysystemforstavudinebiodistribution
AT corderoandresa physiologicallybasedpharmacokineticpbpkmodelofgoldnanoparticlebaseddrugdeliverysystemforstavudinebiodistribution
AT bartneckmatthias physiologicallybasedpharmacokineticpbpkmodelofgoldnanoparticlebaseddrugdeliverysystemforstavudinebiodistribution
AT lanaojosem physiologicallybasedpharmacokineticpbpkmodelofgoldnanoparticlebaseddrugdeliverysystemforstavudinebiodistribution