期刊
BIOMATERIALS
卷 41, 期 -, 页码 141-150出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2014.11.012
关键词
Folic acid receptor; Long-acting nanoformulated antiretroviral therapy; Human immunodeficiency virus type one; Pharmacokinetics; Pharmacodynamics; Non-obese diabetic severe combined; immunodeficient mice
资金
- University of Nebraska Foundation
- National Institutes of Health (NIH), USA [P01 MH64570, RO1 MH104147, P01 DA028555, R01 NS36126, P01 NS31492, 2R01 N5034239, P01 NS43985, P30 MH062261, RO1 AG043540]
Long-acting nanoformulated antiretroviral therapy (nanoART) that targets monocyte-macrophages could improve the drug's half-life and protein-binding capacities while facilitating cell and tissue depots. To this end, ART nanoparticles that target the folic acid (FA) receptor and permit cell-based drug depots were examined using pharmacokinetic and pharmacodynamic (PD) tests. FA receptor-targeted poloxamer 407 nanocrystals, containing ritonavir-boosted atazanavir (ATV/r), significantly increased drug bioavailability and PD by five and 100 times, respectively. Drug particles administered to human peripheral blood lymphocyte reconstituted NOD.Cg-Prkdc(scid)Il2rg(tm1wil)/SzJ mice and infected with HIV-1ADA led to ATV/r drug concentrations that paralleled FA receptor beta staining in both the macrophage-rich parafollicular areas of spleen and lymph nodes. Drug levels were higher in these tissues than what could be achieved by either native drug or untargeted nanoART particles. The data also mirrored potent reductions in viral loads, tissue viral RNA and numbers of HIV-1p24+ cells in infected and treated animals. We conclude that FA-P407 coating of ART nanoparticles readily facilitates drug carriage and antiretroviral responses. (C) 2014 The Authors. Published by Elsevier Ltd.
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