Towards a Maraviroc long-acting injectable nanoformulation.
Eur J Pharm Biopharm
; 138: 92-98, 2019 May.
Article
de En
| MEDLINE
| ID: mdl-29684534
ABSTRACT
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 70â¯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 AUC0-∞ (1959.71 vs 567.17â¯ng.h ml), over a 2.6-fold increase in MVCs terminal half-life (t½) (140.69 vs 53.23â¯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.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
VIH-1 (Virus de l'Immunodéficience Humaine de type 1)
/
Inhibiteurs de fusion du VIH
/
Nanoparticules
/
Maraviroc
Limites:
Animals
Langue:
En
Journal:
Eur J Pharm Biopharm
Sujet du journal:
FARMACIA
/
FARMACOLOGIA
Année:
2019
Type de document:
Article