Polymeric Nanoparticles Affect the Intracellular Delivery, Antiretroviral Activity and Cytotoxicity of the Microbicide Drug Candidate Dapivirine
Polymeric Nanoparticles Affect the Intracellular Delivery, Antiretroviral Activity and Cytotoxicity of the Microbicide Drug Candidate Dapivirine
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DOI：
10.1007/s11095-011-0622-3
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发表时间：
2012-06-01
影响因子：
3.7
通讯作者：
Sarmento, Bruno
中科院分区：
文献类型：
--
作者：
das Neves, Jose;Michiels, Johan;Sarmento, Bruno
为了评价含抗逆转录病毒药物达匹韦林的聚己内酯(PCL)纳米粒的细胞内递送、抗逆转录病毒活性和细胞毒性，用泊洛沙姆338核糖核酸(PEO)、十二烷基硫酸钠(SLS)和十六烷基三甲基溴化铵(CTAB)三种表面修饰剂制备了不同表面性质的达匹韦林纳米粒。纳米颗粒促进细胞内药物传递的能力在不同类型的细胞中进行了评估，这些细胞与经阴道传播艾滋病毒/杀微生物剂的开发有关。此外，在不同的细胞模型中测定了纳米粒的抗逆转录病毒活性以及它们的细胞毒性。载达比韦林的纳米粒很容易被不同的细胞摄取，其特定的动力学取决于细胞类型和纳米粒，从而增强了吞噬细胞的细胞内药物输送。与游离药物相比，不同的纳米颗粒显示出相似或更好的抗病毒活性。抗病毒活性的增强和细胞内药物释放的增加之间存在相关性，特别是当细胞模型接受单一的初始短程治疗时。与CTAB-PCL的高细胞毒性相比，PEO-PCL和SLS-PCL纳米粒始终表现出比游离药物更高的选择性指数。这些结果为PCL纳米粒潜在地影响达匹韦林的毒性和活性提供了证据，这取决于表面工程。因此，这种剂型方法可能是开发下一代杀菌剂的一种有前途的策略。
To assess the intracellular delivery, antiretroviral activity and cytotoxicity of poly(epsilon-caprolactone) (PCL) nanoparticles containing the antiretroviral drug dapivirine.Dapivirine-loaded nanoparticles with different surface properties were produced using three surface modifiers: poloxamer 338 NF (PEO), sodium lauryl sulfate (SLS) and cetyl trimethylammonium bromide (CTAB). The ability of nanoparticles to promote intracellular drug delivery was assessed in different cell types relevant for vaginal HIV transmission/microbicide development. Also, antiretroviral activity of nanoparticles was determined in different cell models, as well as their cytotoxicity.Dapivirine-loaded nanoparticles were readily taken up by different cells, with particular kinetics depending on the cell type and nanoparticles, resulting in enhanced intracellular drug delivery in phagocytic cells. Different nanoparticles showed similar or improved antiviral activity compared to free drug. There was a correlation between increased antiviral activity and increased intracellular drug delivery, particularly when cell models were submitted to a single initial short-course treatment. PEO-PCL and SLS-PCL nanoparticles consistently showed higher selectivity index values than free drug, contrasting with high cytotoxicity of CTAB-PCL.These results provide evidence on the potential of PCL nanoparticles to affect toxicity and activity of dapivirine, depending on surface engineering. Thus, this formulation approach may be a promising strategy for the development of next generation microbicides.