Towards a Maraviroc long-acting injectable nanoformulation

Eur J Pharm Biopharm. 2019 May:138:92-98. doi: 10.1016/j.ejpb.2018.04.009. Epub 2018 Apr 21.


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 AUC0-∞ (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.

Keywords: Intramuscular; Long-Acting Injectable (LAI); Long-Acting Parenteral (LAP); Maraviroc; Nanodispersion; Nanomedicine; Pharmacokinetics; Pre-exposure Prophylaxis (PrEP).

MeSH terms

  • Animals
  • HIV Fusion Inhibitors / administration & dosage*
  • HIV Fusion Inhibitors / chemistry*
  • HIV Infections / drug therapy
  • HIV-1 / drug effects*
  • Injections / methods
  • Injections, Intramuscular / methods
  • Male
  • Maraviroc / administration & dosage*
  • Maraviroc / chemistry*
  • Nanomedicine / methods
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry*
  • Pre-Exposure Prophylaxis / methods
  • Rats
  • Rats, Wistar


  • HIV Fusion Inhibitors
  • Maraviroc