Macrophage targeted nanocarrier delivery systems in HIV therapeutics

ABSTRACT

Introduction

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.

Areas covered

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.

Expert opinion

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.

KEYWORDS:

• HIV
• liposomes
• nanoparticles
• dendrimers
• targeted therapy
• delivery systems
• macrophages

Article highlights

• The crucial involvement of macrophages in the pathogenesis of HIV infection has led to the development of macrophage targeted nanocarrier delivery systems as elimination of viral reservoirs like HIV infected macrophages has emerged to be a fundamental challenge in HIV therapeutics.

• Macrophage targeted nanocarrier delivery systems such as liposomes, ethosomes, polymeric nanoparticles, dendrimers and solid lipid nanoparticles exhibit superior efficacy in comparison to conventional antiretroviral delivery systems.

• The utility of macrophage targeted delivery systems in achieving higher and sustained drug levels in known HIV reservoir sites results in enhanced viral suppression, reduced toxicity, simplified therapeutic regimen, better patient adherence and improved clinical outcomes.

Acknowledgments

The authors acknowledge the support rendered by Mr Chintan Bhavsar in editing this manuscript.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.