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 journalArticle

171 Citations (Scopus)

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

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Macrophages
Indinavir
Drug delivery
Nanoparticles
Bone
Viruses
Pharmaceutical Preparations
Liver
HIV-1
Spleen
Single photon emission computed tomography
Lung
Histology
Pharmacokinetics
Cytoprotection
T-cells
High performance liquid chromatography
Plasma Cells
Single-Photon Emission-Computed Tomography
Medicine

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Development of a macrophage-based nanoparticle platform for antiretroviral drug delivery. / Dou, Huanyu; Destache, Christopher J.; Morehead, Justin R.; Mosley, R Lee; Boska, Michael D.; Kingsley, Jeffrey; Gorantla, Santhi; Poluektova, Larisa Y; Nelson, Jay A.; Chaubal, Mahesh; Werling, Jane; Kipp, James; Rabinow, Barrett E.; Gendelman, Howard Eliot.

In: Blood, Vol. 108, No. 8, 15.10.2006, p. 2827-2835.

Research output: Contribution to journalArticle

Dou, H, Destache, CJ, Morehead, JR, Mosley, RL, Boska, MD, Kingsley, J, Gorantla, S, Poluektova, LY, Nelson, JA, Chaubal, M, Werling, J, Kipp, J, Rabinow, BE & Gendelman, HE 2006, 'Development of a macrophage-based nanoparticle platform for antiretroviral drug delivery', Blood, vol. 108, no. 8, pp. 2827-2835. https://doi.org/10.1182/blood-2006-03-012534
Dou, Huanyu ; Destache, Christopher J. ; Morehead, Justin R. ; Mosley, R Lee ; Boska, Michael D. ; Kingsley, Jeffrey ; Gorantla, Santhi ; Poluektova, Larisa Y ; Nelson, Jay A. ; Chaubal, Mahesh ; Werling, Jane ; Kipp, James ; Rabinow, Barrett E. ; Gendelman, Howard Eliot. / Development of a macrophage-based nanoparticle platform for antiretroviral drug delivery. In: Blood. 2006 ; Vol. 108, No. 8. pp. 2827-2835.
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