Curley, P., Giardiello, M. orcid.org/0000-0003-0560-4711, Liptrott, N.J. et al. (8 more authors) (2017) In vitro characterisation of solid drug nanoparticle compositions of efavirenz in a brain endothelium cell line. Journal of Interdisciplinary Nanomedicine, 2 (3). pp. 157-169. ISSN 2058-3273
Abstract
The antiretroviral drug efavirenz displays many desirable pharmacokinetic properties such as a long half‐life enabling once daily dosing but suffers from central nervous system safety issues. Various nanotechnologies have been explored to mitigate some of the limitations with efavirenz. While there has been progress in increasing the bioavailability, there has been no attempt to assess the impact of increased exposure to efavirenz on central nervous system safety. The uptake of aqueous and solid drug nanoparticle (SDN) formulations of efavirenz was assessed in the human cerebral microvessel endothelial cells/D3 brain endothelial cell line. The mechanisms of uptake were probed using a panel of transport and endocytosis inhibitors. The cellular accumulation of an efavirenz aqueous solution was significantly reduced by amantadine, but this was not observed with SDNs. The uptake of efavirenz SDNs was reduced by dynasore, but concentrations of the efavirenz aqueous solution were not affected. These data indicate that efavirenz is a substrate for transporters in brain endothelial cells (amantadine is an inhibitor of organic cation transporters 1 and 2), and formation of SDNs may bypass this interaction in favour of a mechanism involving dynamin‐mediated endocytosis.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017 John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, (http://creativecommons.org/licenses/by/4.0/) which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | Blood brain barrier; Central nervous system; Efavirenz; Endocytosis; Solid drug nanoparticle |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Engineering (Sheffield) > Department of Materials Science and Engineering (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 11 Feb 2020 16:02 |
Last Modified: | 11 Feb 2020 16:11 |
Status: | Published |
Publisher: | Wiley |
Refereed: | Yes |
Identification Number: | 10.1002/jin2.32 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:156861 |
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