Cell-based drug delivery for improving antiretroviral therapeutic outcomes

During the past decade, our laboratories pioneered the use of monocyte-macrophages as Trojan horses for the uptake, trafficking, and delivery of nanoformulated antiretroviral therapy (nanoART) to improve drug delivery to tissue, cell, and subcellular sites of human immunodeficiency virus infections. Particles were manufactured with excipients and coated with sugars or peptides to facilitate particle uptake and sequestration in mononuclear phagocytes. Particles housed as cellular depots in recycling endosomes and free bioactive medicines dissociated from particles were released over periods of days to weeks. This enabled long-lived drug tissue reservoirs where peripheral monocytes and tissue macrophages activated by the nanoparticles are able to sequester ART for periods of weeks and longer. Indeed, following parenteral injection of the particles high concentrations of drug are found in the reticuloendothelial system with limited systemic toxicities enabling prolonged drug-dosing intervals. Target coating of the particles further facilitated pharmacokinetic and pharmacodynamics improvements over native or naked uncoated particle drug administrations, especially in reaching reservoirs of viral infection, such as the brain, gut, and lymphoid organs. The future of such therapies towards improving drug compliance, diminishing viral resistance, and facilitating residual virus reductions is timely and important and expanded upon within the current review.