Macrophage folate receptor-targeted antiretroviral therapy facilitates drug entry, retention, antiretroviral activities and biodistribution for reduction of human …

P Puligujja, JE McMillan, L Kendrick, T Li… - … , Biology and Medicine, 2013 - Elsevier
P Puligujja, JE McMillan, L Kendrick, T Li, S Balkundi, N Smith, RS Veerubhotla, BJ Edagwa
Nanomedicine: Nanotechnology, Biology and Medicine, 2013Elsevier
Macrophages serve as vehicles for the carriage and delivery of polymer-coated
nanoformulated antiretroviral therapy (nanoART). Although superior to native drug, high
drug concentrations are required for viral inhibition. Herein, folate-modified ritonavir-boosted
atazanavir (ATV/r)-encased polymers facilitated macrophage receptor targeting for
optimizing drug dosing. Folate coating of nanoART ATV/r significantly enhanced cell uptake,
retention and antiretroviral activities without altering cell viability. Enhanced retentions of …
Abstract
Macrophages serve as vehicles for the carriage and delivery of polymer-coated nanoformulated antiretroviral therapy (nanoART). Although superior to native drug, high drug concentrations are required for viral inhibition. Herein, folate-modified ritonavir-boosted atazanavir (ATV/r)-encased polymers facilitated macrophage receptor targeting for optimizing drug dosing. Folate coating of nanoART ATV/r significantly enhanced cell uptake, retention and antiretroviral activities without altering cell viability. Enhanced retentions of folate-coated nanoART within recycling endosomes provided a stable subcellular drug depot. Importantly, up to a five-fold enhanced plasma and tissue drug levels followed folate-coated formulation injection in mice. Folate polymer encased ATV/r improves nanoART pharmacokinetics bringing the technology one step closer to human use.
From the Clinical Editor
This team of authors describes a novel method for macrophage folate receptor-targeted antiretroviral therapy. Atazanvir entry, retention, and antiretroviral activities were superior using the presented method, and so was its biodistribution, enabling a more efficient way to address human immunodeficiency virus infections, with a hoped for clinical application in the near future.
Elsevier