Small magnetite antiretroviral therapeutic nanoparticle probes for MRI of drug biodistribution

Dongwei Guo, Tianyuzi Li, Jo Ellyn Mcmillan, Balasrinivasa R. Sajja, Pavan Puligujja, Michael D. Boska, Howard E. Gendelman, Xin Ming Liu

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Aim: 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. Materials & 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. Conclusion: SMART can permit rapid assessment of drug tissue concentrations in viral reservoirs.

Original languageEnglish (US)
Pages (from-to)1341-1352
Number of pages12
JournalNanomedicine
Volume9
Issue number9
DOIs
StatePublished - Jul 1 2014

Keywords

  • HIV
  • macrophage
  • monocyte
  • nanomedicine
  • nanoparticles
  • small magnetite antiretroviral therapy

ASJC Scopus subject areas

  • Bioengineering
  • Development
  • Biomedical Engineering
  • General Materials Science
  • Medicine (miscellaneous)

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