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 Y Poluektova, Jay A. Nelson, Mahesh Chaubal, Jane Werling, James Kipp, Barrett E. Rabinow, Howard Eliot Gendelman

Research output: Contribution to journalArticlepeer-review

188 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

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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