Curley, P and Giardiello, M and Liptrott, NJ and Dickens, D and Moss, DM and Hobson, J and Savage, AC and McDonald, T and Siccardi, M and Rannard, S and Owen, A (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

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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.

Item Type: Article
Additional Information: This is the final published version of the article (version of record). It first appeared online via Wiley at http://doi.org/10.1002/jin2.32 - please refer to any applicable terms of use of the publisher.
Subjects: R Medicine > RS Pharmacy and materia medica
Divisions: Faculty of Medicine and Health Sciences > School of Pharmacy
Depositing User: Symplectic
Date Deposited: 21 Nov 2017 15:21
Last Modified: 21 Nov 2017 15:31
URI: http://eprints.keele.ac.uk/id/eprint/4249

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