Formulation of Biocompatible Targeted ECO/siRNA Nanoparticles with Long-Term Stability for Clinical Translation of RNAi
Formulation of Biocompatible Targeted ECO/siRNA Nanoparticles with Long-Term Stability for Clinical Translation of RNAi
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DOI：
10.1089/nat.2019.0784
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发表时间：
2019-05-28
影响因子：
4
通讯作者：
Lu, Zheng-Rong
中科院分区：
文献类型：
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作者：
Ayat, Nadia R.;Sun, Zhanhu;Lu, Zheng-Rong
基于纳米颗粒的siRNA制剂在储存期间经常遭受聚集和功能丧失。我们在这项研究中报告了一种冷冻靶向RGD-聚乙二醇（PEG）-ECO/Si β 3纳米颗粒制剂，具有延长的保质期和保留的纳米颗粒功能。靶向RGD-PEG-ECO/si β 3纳米颗粒通过RGD-PEG-马来酰亚胺、ECO和siRNA的逐步自组装形成。纳米颗粒的直径为224.5 +/- 9.41 nm，在水中的ζ电位为45.96 +/- 3.67 mV，在盐水溶液中的尺寸为234.34 +/- 3.01 nm，ζ电位接近中性。蔗糖的添加不影响它们的尺寸和ζ电位，并且基本上保持了靶向纳米颗粒的冷冻和冻干制剂的完整性和生物活性。含有低至5%蔗糖的冷冻制剂保留了纳米颗粒的完整性（90% siRNA包封）、尺寸分布（多分散指数[PDI]）
Nanoparticle based siRNA formulations often suffer from aggregation and loss of function during storage. We in this study report a frozen targeted RGD-polyethylene glycol (PEG)-ECO/si beta 3 nanoparticle formulation with a prolonged shelf life and preserved nanoparticle functionality. The targeted RGD-PEG-ECO/si beta 3 nanoparticles are formed by step-wised self-assembly of RGD-PEG-maleimide, ECO, and siRNA. The nanoparticles have a diameter of 224.5 +/- 9.41 nm and a zeta potential to 45.96 +/- 3.67 mV in water and a size of 234.34 +/- 3.01 nm and a near neutral zeta potential in saline solution. The addition of sucrose does not affect their size and zeta potential and substantially preserves the integrity and biological activities of frozen and lyophilized formulations of the targeted nanoparticles. The frozen formulation with as low as 5% sucrose retains nanoparticle integrity (90% siRNA encapsulation), size distribution (polydispersity index [PDI]