Portal de Periódicos da CAPES

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

2006; Elsevier BV; Volume: 108; Issue: 8 Linguagem: Inglês

10.1182/blood-2006-03-012534

1528-0020

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

HIV/AIDS Research and Interventions

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.