期刊
BLOOD
卷 108, 期 8, 页码 2827-2835出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2006-03-012534
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资金
- NCRR NIH HHS [P20 RR015635, P20 RR 15635] Funding Source: Medline
- NIMH NIH HHS [P01 MH 64570, P01 MH064570] Funding Source: Medline
- NINDS NIH HHS [P01 NS 31492, R37 NS036126, 2R37 NS 36126, P01 NS 43985, P01 NS031492, R01 NS034239, 2R01 NS 034239, P01 NS043985] Funding Source: Medline
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.
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