title: Macrophage endocytic trafficking of antiretroviral nanoparticles.
abstract: OBJECTIVE
  Nanoformulated antiretroviral therapy can improve drug compliance for people infected with HIV. Additional benefits would include specific drug deliveries to viral reservoirs and reduction in systemic toxicities.
  
  
  METHODS
  In this article, we describe mechanisms of crystalline antiretroviral nanoparticle (NP) uptake, intracellular trafficking and release in human monocyte-derived macrophages.
  
  
  RESULTS
  Following clathrin-dependent endocytosis NPs bypassed lysosomal degradation by sorting from early endosomes to recycling endosome pathways. Disruption of this pathway by siRNAs or brefeldin-A impaired particle release. Proteomic and biological analysis demonstrated that particle recycling was primarily Rab11 regulated. Particles were released intact and retained complete antiretroviral efficacy.
  
  
  CONCLUSIONS
  These results suggest possible pathways of subcellular transport of antiretroviral nanoformulations that preserve both particle integrity and antiretroviral activities demonstrating the potential utility of this approach for targeted drug delivery.
authors.affiliation: Department of Pharmacology & Experimental Neuroscience, University of Nebraska Medical Center, 985800 Nebraska Medical Center, Omaha, NE 68198-5880, USA.
authors.forename: Irena
authors.initials: I
authors.lastname: Kadiu
authors.forename: Ari
authors.initials: A
authors.lastname: Nowacek
authors.forename: Joellyn
authors.initials: J
authors.lastname: McMillan
authors.forename: Howard E
authors.initials: HE
authors.lastname: Gendelman
mesh_terms: D001692:Biological Transport; D004705:Endocytosis / Q000502:physiology; D017320:HIV Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects / Q000472:pathogenicity; D006801:Humans; D007150:Immunohistochemistry; D008247:Lysosomes / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D008954:Models, Biological; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D036103:Nanotechnology; D019438:Ritonavir / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D017320:HIV Protease Inhibitors; D019438:Ritonavir