Pharmacotoxicology of monocyte-macrophage nanoformulated antiretroviral drug uptake and carriage.
Pharmacotoxicology of monocyte-macrophage nanoformulated antiretroviral drug uptake and carriage.
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DOI：
10.3109/17435390.2010.541292
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发表时间：
2011-12
期刊：
影响因子：
5
通讯作者：
Kanmogne GD
中科院分区：
文献类型：
--
作者：
Bressani RF;Nowacek AS;Singh S;Balkundi S;Rabinow B;McMillan J;Gendelman HE;Kanmogne GD
尽管抗逆转录病毒疗法（ART）已广泛使用了15年，但其药代动力学特性仍存在固有的局限性。我们的实验室开创了一种通过单核细胞-巨噬细胞携带纳米药物包封颗粒（nanoART）来改善ART递送的方法。为此，我们先前的工作试图优化nanoART的尺寸、结构和物理性质，以用于细胞摄取和抗逆转录病毒活性。为了测试茚地那韦、利托那韦和依法韦仑制剂的功能后果，我们研究了人单核细胞和巨噬细胞细胞毒性与nanoART剂量、大小、表面活性剂和制剂之间的关系。湿磨颗粒对单核细胞-巨噬细胞的细胞毒性显著高于通过均质化制备的颗粒;同时诱导肿瘤坏死因子-α。有趣的是，0.5mM茚地那韦和利托那韦以及0.1mM和0.5mM依法韦仑的纯混悬液也被证明具有细胞毒性。个别表面活性剂和配制氟康唑既不影响细胞功能或活力。尽管nanoART没有改变脑紧密连接蛋白ZO-2和occludin，但0.5mM利托那韦制剂确实改变了脑跨内皮电阻。这些结果强调了在人体评价之前评价nanoART的理化和功能特性的重要性。
Limitations inherent to antiretroviral therapy (ART) in its pharmacokinetic properties remain despite over 15 years of broad use. Our laboratory has pioneered a means to improve ART delivery through monocyte-macrophage carriage of nanoformulated drug-encapsulated particles (nanoART). To this end, our prior works sought to optimize nanoART size, structure, and physical properties for cell uptake and antiretroviral activities. To test the functional consequences of indinavir, ritonavir, and efavirenz formulations we investigated relationships between human monocyte and macrophage cytotoxicities and nanoART dose, size, surfactant, and preparation. Wet-milled particles were significantly more cytotoxic to monocytes-macrophages than those prepared by homogenization; with concurrent induction of tumor necrosis factor-alpha. Interestingly, pure suspensions of indinavir and ritonavir at 0.5mM, and efavirenz at 0.1mM and 0.5mM also proved cytotoxic. Individual surfactants and formulated fluconazole neither affected cell function or viability. Although nanoART did not alter brain tight junction proteins ZO-2 and occludin, 0.5mM ritonavir formulations did alter brain transendothelial electric resistance. These results underscore the importance of evaluating the physicochemical and functional properties of nanoART before human evaluations.
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DOI：
10.2217/nnm.09.38
发表时间：
2009-07
期刊：
Nanomedicine (London, England)
影响因子：
--
作者：
Nowacek A;Gendelman HE
通讯作者：
Gendelman HE
影响因子：
5.5
作者：
Muthu, M. S.;Singh, S.
通讯作者：
Singh, S.
影响因子：
5.5
作者：
Gorantla, Santhi;Dou, Huanyu;Mosley, R. Lee
通讯作者：
Mosley, R. Lee
影响因子：
1
作者：
Kiertiburanakul, Sasisopin;Sungkanuparph, Somnuek
通讯作者：
Sungkanuparph, Somnuek
影响因子：
3.7
作者：
Dou, Huanyu;Morehead, Justin;Gendelman, Howard E.
通讯作者：
Gendelman, Howard E.