Inhalation Properties and Stability of Nebulized Naked siRNA Solution for Pulmonary Therapy
Inhalation Properties and Stability of Nebulized Naked siRNA Solution for Pulmonary Therapy
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DOI：
10.1248/cpb.c15-00615
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发表时间：
2016-01-01
影响因子：
1.7
通讯作者：
Takeuchi, Hirofumi
中科院分区：
文献类型：
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作者：
Tahara, Kohei;Hashimoto, Wakana;Takeuchi, Hirofumi
先前已经研究了使用无载体的裸的未修饰的小干扰RNA（N-siRNA）作为肺部治疗。然而，关于含N-siRNA液滴的稳定性和空气动力学粒径知之甚少;雾化器尚未针对N-siRNA溶液进行优化。因此，在本研究中，我们研究了使用雾化吸入用于肺部治疗的N-siRNA溶液的可行性。根据雾化后的siRNA完整性评估各种雾化器和N-siRNA浓度，并检查包括空气动力学粒度的吸入特性。与超声雾化器、空气喷射雾化器和振动网孔雾化器相比，N-siRNA完整性不受雾化影响。因此，在进一步的实验中，使用采用飞行时间原理的空气动力学粒度仪（APS）或级联撞击器评估和筛选具有不同雾化器和N-siRNA浓度的N-siRNA气溶胶的性能。来自振动筛雾化器的含N-siRNA液滴的平均质量空气动力学直径倾向于随着N-siRNA浓度的增加而降低，反映了N-siRNA溶液对表面张力的影响，如接触角所示。这些数据表明APS仪器用于研究包括siRNA在内的昂贵药物的雾化特性的实用性，并且可以促进N-siRNA吸入制剂的开发。
The use of naked unmodified small interfering RNA (N-siRNA) without vector has previously been investigated as a pulmonary therapy. However, little is known regarding stabilities and aerodynamic particle sizes of N-siRNA-containing droplets; nebulizers have not yet been optimized for N-siRNA solutions. Thus, in this study, we investigated the feasibility of inhaled N-siRNA solutions for pulmonary therapy using nebulization. Various nebulizers and N-siRNA concentrations were assessed in terms of siRNA integrity after nebulization, and inhalation properties including aerodynamic particle size were examined. In comparison with ultrasonic-, air-jet-, and vibrating-mesh nebulizers, N-siRNA integrity was not affected by nebulization. Thus, in further experiments, performances of N-siRNA aerosols with different nebulizers and N-siRNA concentrations were evaluated and screened using an aerodynamic particle sizer (APS) which employed the time-of-flight principle or a cascade impactor. Mean mass aerodynamic diameters of N-siRNA-containing droplets from vibrating-mesh nebulizers tended to decrease with increasing N-siRNA concentrations, reflecting the influence of N-siRNA solutions on surface tension, as indicated by contact angles. These data indicate the utility of APS instruments for investigating the nebulized characteristics of expensive drugs including siRNAs and may facilitate the development of N-siRNA inhalation formulations.