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

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

来源：Blood, 2006, 108(8): 2827-2835.

DOI：10.1182/blood-2006-03-012534

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 mu M 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.

• 出版日期2006-10-15