Novel elvitegravir nanoformulation approach to suppress the viral load in HIV-infected macrophages.
Novel elvitegravir nanoformulation approach to suppress the viral load in HIV-infected macrophages.
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DOI：
10.1016/j.bbrep.2017.10.005
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发表时间：
2017-12
影响因子：
2.7
通讯作者：
Kumar S
中科院分区：
文献类型：
--
作者：
Gong Y;Chowdhury P;Midde NM;Rahman MA;Yallapu MM;Kumar S
单核细胞是HIV-1的避难所，这种病毒很难被消灭。因此，单核细胞中有效的病毒抑制对于有效的抗逆转录病毒治疗（ART）至关重要。本研究的重点是利用纳米制剂优化抗逆转录病毒药物对hiv感染单核细胞的疗效。采用纳米沉淀法制备了聚乳酸-羟基乙酸（PLGA）基埃维替韦纳米颗粒（PLGA- evg）。利用透射电子显微镜、动态光散射和红外光谱对PLGA-EVG的理化性质进行了表征。采用荧光显微镜和流式细胞术进行细胞摄取研究。所有体外实验均使用hiv感染的单核细胞系U1和hiv感染的原代巨噬细胞进行。采用LC-MS/MS进行液相色谱定量。采用p24酶联免疫吸附法检测HIV病毒复制。我们开发了一种PLGA-EVG纳米颗粒配方，透射电镜下其粒径为~ 47 nm，动态光散射下zeta电位为~ 6.74 mV。这些纳米颗粒在单核细胞中表现出时间和浓度依赖性。PLGA-EVG制剂的细胞内EVG内化率比对照组（单独EVG）高2倍。PLGA-EVG纳米颗粒在较长一段时间内也表现出优于对照组的病毒抑制作用。基于plga的EVG纳米制剂增加了EVG的细胞内摄取，并增强了HIV感染巨噬细胞中的病毒抑制，这表明它有可能改善单核细胞中的HIV治疗。
Monocytes serve as sanctuary sites for HIV-1 from which virus is difficult to be eliminated. Therefore, an effective viral suppression in monocytes is critical for effective antiretroviral therapy (ART). This study focuses on a new strategy using nanoformulation to optimize the efficacy of ART drugs in HIV-infected monocytes. Poly(lactic-co-glycolic acid) (PLGA)-based elvitegravir nanoparticles (PLGA-EVG) were prepared by nano-precipitation technique. The physicochemical properties of PLGA-EVG were characterized using transmission electron microscopy, dynamic light scattering, and Fourier-transform infrared spectroscopy. Cellular uptake study was performed by fluorescence microscopy and flow cytometry. All in vitro experiments were performed by using HIV-infected monocytic cell lines U1 and HIV-infected primary macrophages. Elvitegravir quantification was performed using LC-MS/MS. HIV viral replication was assessed by using p24 ELISA. We developed a PLGA-EVG nanoparticle formulation with particle size of ~ 47 nm from transmission electron microscopy and zeta potential of ~ 6.74 mV from dynamic light scattering. These nanoparticles demonstrated a time- and concentration-dependent uptakes in monocytes. PLGA-EVG formulation showed a ~ 2 times higher intracellular internalization of EVG than control group (EVG alone). PLGA-EVG nanoparticles also demonstrated superior viral suppression over control for a prolonged period of time. PLGA-based EVG nanoformulation increased the intracellular uptake of EVG, as well as enhanced viral suppression in HIV-infected macrophages, suggesting its potential for improved HIV treatment in monocytic cells.