title: Small magnetite antiretroviral therapeutic nanoparticle probes for MRI of drug biodistribution.
abstract: OBJECTIVE
  Drug toxicities, compliance and penetrance into viral reservoirs have diminished the efficacy of long-term antiretroviral therapy (ART) for treatment of HIV infection. Cell-targeted nanoformulated ART was developed to improve disease outcomes. However, rapid noninvasive determination of drug biodistribution is unrealized. To this end, small magnetite ART (SMART) nanoparticles can provide assessments of ART biodistribution by MRI.
  
  
  METHODS
  Poly(lactic-co-glycolic acid), 1,2-distearoyl-sn-glycero-3-phosphocholine- and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-(methoxy-PEG 2000)-encased particles were synthesized with atazanavir (ATV) and magnetite. Uptake and retention of ATV and magnetite administered at 3:1 ratios (weight/weight) were determined in human monocyte-derived macrophages and mice.
  
  
  RESULTS
  SMART particles were taken up and retained in macrophages. In mice, following parenteral SMART injection, magnetite and drug biodistribution paralleled one another with MRI signal intensity greatest in the liver and spleen at 24 h. Significantly, ATV and magnetite levels correlated.
  
  
  CONCLUSIONS
  SMART can permit rapid assessment of drug tissue concentrations in viral reservoirs.
authors.affiliation: Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198-5830, USA.
authors.forename: Dongwei
authors.initials: D
authors.lastname: Guo
authors.forename: Tianyuzi
authors.initials: T
authors.lastname: Li
authors.forename: JoEllyn
authors.initials: J
authors.lastname: McMillan
authors.forename: Balasrinivasa R
authors.initials: BR
authors.lastname: Sajja
authors.forename: Pavan
authors.initials: P
authors.lastname: Puligujja
authors.forename: Michael D
authors.initials: MD
authors.lastname: Boska
authors.forename: Howard E
authors.initials: HE
authors.lastname: Gendelman
authors.forename: Xin-Ming
authors.initials: XM
authors.lastname: Liu
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism; D015497:HIV-1; D006801:Humans; D008099:Liver / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D050997:Nanomedicine; D010316:Particle Size; D013154:Spleen / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D019380:Anti-HIV Agents; D004337:Drug Carriers; D058185:Magnetite Nanoparticles
keywords: HIV; macrophage; monocyte; nanomedicine; nanoparticles; small magnetite antiretroviral therapy
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