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

作者：Puligujja Pavan; McMillan JoEllyn; Kendrick Lindsey; Li Tianyuzi; Balkundi Shantanu; Smith Nathan; Veerubhotla Ram S; Edagwa Benson J; Kabanov Alexander V; Bronich Tatiana; Gendelman Howard E^*; Liu Xin Ming

来源：Nanomedicine: Nanotechnology, Biology and Medicine , 2013, 9(8): 1263-1273.

DOI：10.1016/j.nano.2013.05.003

• Human immunodeficiency virus
• NanoART
• ATV/r
• Targeted drug delivery
• Folate
• Poloxamer 407
• Macrophages

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. %26lt;br%26gt;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.

• 出版日期2013-11