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 (Fe3O4; 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.
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This work was supported in part by National Institute on Drug Abuse grants R01-DA012366, R01-DA014218, R01-DA015628, R01-DA021537, R37-DA025576, and R01-DA027049.
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Saiyed, Z.M., Gandhi, N.H. & Nair, M.P.N. AZT 5′-triphosphate nanoformulation suppresses human immunodeficiency virus type 1 replication in peripheral blood mononuclear cells. Journal of NeuroVirology 15, 343–347 (2009). https://doi.org/10.1080/13550280903062813
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DOI: https://doi.org/10.1080/13550280903062813