Efficiency of nanoparticles as a carrier system for antiviral agents in human immunodeficiency virus-infected human monocytes/macrophages in vitro.

Polyhexylcyanoacrylate nanoparticles loaded with either the human immunodeficiency virus (HIV) protease inhibitor saquinavir (Ro 31-8959) or the nucleoside analog zalcitabine (2',3'-dideoxycytidine) were prepared by emulsion polymerization and tested for antiviral activity in primary human monocytes/macrophages in vitro. Both nanoparticulate formulations led to a dose-dependent reduction of HIV type 1 antigen production. While nanoparticle-bound zalcitabine showed no superiority to an aqueous solution of the drug, a significantly higher efficacy was observed with saquinavir-loaded nanoparticles. In acutely infected cells, an aqueous solution of saquinavir showed little antiviral activity at concentrations below 10 nM, whereas the nanoparticulate formulation exhibited a good antiviral effect at a concentration of 1 nM and a still-significant antigen reduction at 0.1 nM (50% inhibitory concentrations = 4.23 nM for the free drug and 0.39 nM for the nanoparticle-bound drug). At a concentration of 100 nM, saquinavir was completely inactive in chronically HIV-infected macrophages, but when bound to nanoparticles it caused a 35% decrease in antigen production. Using nanoparticles as a drug carrier system could improve the delivery of antiviral agents to the mononuclear phagocyte system in vivo, overcoming pharmacokinetic problems and enhancing the activities of drugs for the treatment of HIV infection and AIDS.