UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Population pharmacokinetic modelling of indium-based quantum dot nanoparticles: preclinical in vivo studies

Yaghini, E; Tacconi, E; Pilling, A; Rahman, P; Broughton, J; Naasani, I; Keshtgar, MRS; ... Della Pasqua, O; + view all (2021) Population pharmacokinetic modelling of indium-based quantum dot nanoparticles: preclinical in vivo studies. European Journal of Pharmaceutical Sciences , 157 , Article 105639. 10.1016/j.ejps.2020.105639. Green open access

[thumbnail of Della Pasqua_1-s2.0-S0928098720304279-main.pdf]
Preview
Text
Della Pasqua_1-s2.0-S0928098720304279-main.pdf - Published version

Download (11MB) | Preview

Abstract

There is considerable interest in biomedical applications of quantum dot (QD) nanoparticles, in particular their use as imaging agents for diagnostic applications. In order to investigate the in vivo biodistribution and the potential toxicity of quantum dots (QDs), it is crucial to develop pharmacokinetic (PK) models as basis for prediction of QDs exposure profiles over time. Here, we investigated the in vivo biodistribution of novel indium-based QDs in mice for up to three months after intravenous administration and subsequently developed a translational population PK model to scale findings to humans. This evaluation was complemented by a comprehensive overview of the in vivo toxicology of QDs in rats. The QDs were primarily taken up by the liver and spleen and were excreted via hepatobiliary and urinary pathways. A non-linear mixed effects modelling approach was used to describe blood and organ disposition characteristics of QDs using a multi-compartment PK model. The observed blood and tissue exposure to QDs was characterised with an acceptable level of accuracy at short and long-term. Of note is the fast distribution of QDs from blood into liver and spleen in the first 24 h post-injection (half-life of 28 min) followed by a long elimination profile (half-life range: 47-90 days). This is the first study to assess the PK properties of QDs using a population pharmacokinetic approach to analyse in vivo preclinical data. No organ damage was observed following systemic administration of QDs at doses as high as 48 mg/kg at 24 h, 1 week and 5 weeks post-injection. In conjunction with the data arising from the toxicology experiments, PK parameter estimates provide insight into the potential PK properties of QDs in humans, which ultimately allow prediction of their disposition and enable optimisation of the design of first-in-human QDs studies.

Type: Article
Title: Population pharmacokinetic modelling of indium-based quantum dot nanoparticles: preclinical in vivo studies
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.ejps.2020.105639
Publisher version: https://doi.org/10.1016/j.ejps.2020.105639
Language: English
Additional information: This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: nanoparticles, quantum dots, pharmacokinetics, population pharmacokinetic modelling, biodistribution, toxicology
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmacology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Surgical Biotechnology
URI: https://discovery.ucl.ac.uk/id/eprint/10114295
Downloads since deposit
10Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item