Macrophage targeted nanocarrier delivery systems in HIV therapeutics

Human immunodeficiency virus (HIV) targets and modulates the immune system increasing the risk of other associated infections. Highly active antiretroviral therapy (HAART) has significantly improved AIDS-associated morbidity, but has limitations of adverse effects, frequent dosing regimen leading to medical non-adherence. Drug delivery systems that target HIV reservoirs could potentially reduce dose-dependent toxicity and the duration of treatment. The major cellular HIV reservoirs are macrophages and CD4⁺ T cells with macrophages being responsible for carrying and spreading the virus. The crucial involvement of macrophages in the pathogenesis of HIV infection has led to development of macrophage targeted nanocarrier delivery systems.

Eradication of viral reservoirs like HIV-infected macrophages has emerged to be a fundamental barrier and challenge for complete eradication of HIV from the immune system. Literature reports several macrophage targeted nanocarrier delivery systems developed as either functionalized or non-functionalized formulations such as liposomes, ethosomes, polymeric nanoparticles, dendrimers, and solid lipid nanoparticles showcasing superior efficacy over the conventional antiretroviral delivery systems.

The development of fixed dose combination of antiretroviral drugs into macrophage targeted delivery systems should factor in the inherent plasticity and heterogeneity of macrophages that is dependent on their microenvironment. A rational selection of nanocarriers will facilitate selectivity and enhanced efficacy of antiretroviral drugs accompanied by reduced dosing and toxicity. Such macrophage targeted delivery systems would positively impact the therapeutic outcomes in the management of HIV infection.