Towards a Maraviroc long-acting injectable nanoformulation

Tatham, Lee M ORCID: 0000-0001-9448-8876, Savage, Alison C ORCID: 0000-0002-5312-9946, Dwyer, Andrew, Siccardi, Marco ORCID: 0000-0002-3539-7867, Scott, Trevor, Vourvahis, Manoli, Clark, Andrew, Rannard, Steven P ORCID: 0000-0002-6946-1097 and Owen, Andrew ORCID: 0000-0002-9819-7651
(2019) Towards a Maraviroc long-acting injectable nanoformulation. EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, 138. pp. 92-98.

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Suboptimal adherence to antiretroviral (ARV) therapy can lead to insufficient drug exposure leading to viral rebound and increased likelihood of resistance. This has driven the development of long-acting injectable (LAI) formulations which may mitigate some of these problems. Maraviroc (MVC) is an orally dosed CCR5 antagonist approved for use in patients infected with CCR5-trophic HIV-1. MVC prevents viral entry into host cells, is readily distributed to biologically relevant tissues and has an alternative resistance profile compared to more commonly used therapies. This makes a MVC LAI formulation particularly appealing for implementation in Pre-Exposure Prophylaxis (PrEP). A 70 wt% MVC-loaded nanodispersion stabilised with polyvinyl alcohol (PVA) and sodium 1,4-bis(2-ethylhexoxy)-1,4-dioxobutane-2-sulfonate (AOT) was prepared using emulsion-templated freeze-drying. In vitro release rate studies revealed over a 22% decrease in MVC release rate constant across a size selective membrane compared with an aqueous solution of MVC (<5% DMSO). Pharmacokinetic studies in rats were subsequently carried out following intramuscular injection of either the nanodispersion or an aqueous MVC preparation (<5% DMSO). Results demonstrated over a 3.4-fold increase in AUC<sub>0-∞</sub> (1959.71 vs 567.17 ng.h ml), over a 2.6-fold increase in MVCs terminal half-life (t½) (140.69 vs 53.23 h) and MVC concentrations present up to 10-days. These data support development of a MVC LAI formulation with potential application in HIV therapy or prevention.

Item Type: Article
Uncontrolled Keywords: Maraviroc, Long-Acting Injectable (LAI), Long-Acting Parenteral (LAP), Intramuscular, Nanodispersion, Nanomedicine, Pharmacokinetics, Pre-exposure Prophylaxis (PrEP)
Depositing User: Symplectic Admin
Date Deposited: 04 Jul 2018 14:30
Last Modified: 08 Feb 2024 17:24
DOI: 10.1016/j.ejpb.2018.04.009
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