AZT 5'-triphosphate nanoformulation suppresses human immunodeficiency virus type 1 replication in peripheral blood mononuclear cells

J Neurovirol. 2009 Jul;15(4):343-7. doi: 10.1080/13550280903062813.

Abstract

Inefficient cellular phosphorylation of nucleoside and nucleotide analog reverse transcriptase inhibitors (NRTIs) to their active nucleoside 5'-triphosphate (NTPs) form is one of the limitations for human immunodeficiency virus (HIV) therapy. We report herein direct binding of 3'-azido-3'-deoxythymidine-5'-triphosphate (AZTTP) onto magnetic nanoparticles (Fe(3)O(4); magnetite) due to ionic interaction. This magnetic nanoparticle bound AZTTP (MP-AZTTP) completely retained its biological activity as assessed by suppression of HIV-1 replication in peripheral blood mononuclear cells. The developed MP-AZTTP nanoformulation can be used for targeting active NRTIs to the brain by application of an external magnetic force and thereby eliminate the brain HIV reservoir and help to treat NeuroAIDS.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Anti-HIV Agents / pharmacology
  • Blood-Brain Barrier
  • Cells, Cultured
  • Dideoxynucleotides / chemistry
  • Dideoxynucleotides / pharmacology*
  • Drug Carriers / administration & dosage
  • Drug Carriers / chemistry
  • Drug Compounding / methods*
  • Electromagnetic Fields
  • Ferrosoferric Oxide / administration & dosage
  • Ferrosoferric Oxide / chemistry*
  • Ferrosoferric Oxide / pharmacology*
  • Humans
  • Leukocytes, Mononuclear / virology
  • Nanomedicine / methods
  • Thymine Nucleotides / chemistry
  • Thymine Nucleotides / pharmacology*
  • Virus Replication / drug effects*
  • Zidovudine / analogs & derivatives*
  • Zidovudine / chemistry
  • Zidovudine / pharmacology

Substances

  • Anti-HIV Agents
  • Dideoxynucleotides
  • Drug Carriers
  • Thymine Nucleotides
  • Zidovudine
  • 3'-azido-3'-deoxythymidine 5'-triphosphate
  • Ferrosoferric Oxide