Laboratory investigations for the morphologic, pharmacokinetic, and anti-retroviral properties of indinavir nanoparticles in human nomocyte-derived macrophages
Laboratory investigations for the morphologic, pharmacokinetic, and anti-retroviral properties of indinavir nanoparticles in human nomocyte-derived macrophages
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DOI：
10.1016/j.virol.2006.08.012
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发表时间：
2007-02-05
期刊：
影响因子：
3.7
通讯作者：
Gendelman, Howard E.
中科院分区：
文献类型：
--
作者：
Dou, Huanyu;Morehead, Justin;Gendelman, Howard E.
抗逆转录病毒疗法（ART）的有效性取决于其清除持续人类免疫缺陷病毒（HIV）感染库的最终能力。我们推断，单核吞噬细胞是病毒传播的主要载体，也可以充当 ART 转运蛋白，从而改善治疗指数。制备了纳米颗粒茚地那韦 (NP-IDV) 制剂，并将其吸收到人单核细胞源性巨噬细胞 (MDM) 的液泡中并从液泡中释放。单次 NP-IDV 剂量后，MDM 内外的药物水平在 6 天内保持恒定，没有细胞毒性。与相同药物水平的游离可溶性 IDV 相比，施用 NP-IDV 显着阻断了 HIV-1 感染后多核巨细胞的诱导、培养液中逆转录酶活性的产生以及细胞相关的 HIV-1p24 抗原。这些数据为使用基于巨噬细胞的 NP 递送系统治疗人类 HIV-1 感染提供了“概念证明”。 (c) 2006 Elsevier Inc. 保留所有权利。
The effectiveness of anti-retroviral therapies (ART) depends on its ultimate ability to clear reservoirs of continuous human immunodeficiency virus (HIV) infection. We reasoned that a principal vehicle for viral dissemination, the mononuclear phagocytes could also serve as an ART transporter and as such improve therapeutic indices. A nanoparticle-indinavir (NP-IDV) formulation was made and taken up into and released from vacuoles of human monocyte-derived macrophages (MDM). Following a single NP-IDV dose, drug levels within and outside MDM remained constant for 6 days without cytotoxicity. Administration of NP-IDV when compared to equal drug levels of free soluble IDV significantly blocked induction of multinucleated giant cells, production of reverse transcriptase activity in culture fluids and cell-associated HIV-1p24 antigens after HIV-1 infection. These data provide "proof of concept" for the use of macrophage-based NP delivery systems for human HIV-1 infections. (c) 2006 Elsevier Inc. All rights reserved.