Development of a macrophage-based nanoparticle platform for antiretroviral drug delivery

Huanyu Dou, Christopher J. Destache, Justin R. Morehead, R. Lee Mosley, Michael D. Boska, Jeffrey Kingsley, Santhi Gorantla, Larisa Poluektova, Jay A. Nelson, Mahesh Chaubal, Jane Werling, James Kipp, Barrett E. Rabinow, Howard E. Gendelman

Research output: Contribution to journalArticle

179 Scopus citations

Abstract

Complex dosing regimens, costs, side effects, biodistribution limitations, and variable drug pharmacokinetic patterns have affected the long-term efficacy of antiretroviral medicines. To address these problems, a nanoparticle indinavir (NP-IDV) formulation packaged into carrier bone marrow-derived macrophages (BMMs) was developed. Drug distribution and disease outcomes were assessed in immune-competent and human immunodeficiency virus type 1 (HIV-1)-infected humanized immune-deficient mice, respectively. In the former, NP-IDV formulation contained within BMMs was adoptively transferred. After a single administration, single-photon emission computed tomography, histology, and reverse-phase-high-performance liquid chromatography (RP-HPLC) demonstrated robust lung, liver, and spleen BMMs and drug distribution. Tissue and sera IDV levels were greater than or equal to 50 μM for 2 weeks. NP-IDV-BMMs administered to HIV-1-challenged humanized mice revealed reduced numbers of virus-infected cells in plasma, lymph nodes, spleen, liver, and lung, as well as, CD4+ T-cell protection. We conclude that a single dose of NP-IDV, using BMMs as a carrier, is effective and warrants consideration for human testing.

Original languageEnglish (US)
Pages (from-to)2827-2835
Number of pages9
JournalBlood
Volume108
Issue number8
DOIs
StatePublished - Oct 15 2006

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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  • Cite this

    Dou, H., Destache, C. J., Morehead, J. R., Mosley, R. L., Boska, M. D., Kingsley, J., Gorantla, S., Poluektova, L., Nelson, J. A., Chaubal, M., Werling, J., Kipp, J., Rabinow, B. E., & Gendelman, H. E. (2006). Development of a macrophage-based nanoparticle platform for antiretroviral drug delivery. Blood, 108(8), 2827-2835. https://doi.org/10.1182/blood-2006-03-012534