Effect of thermal and shear stresses in the spray drying process on the stability of siRNA dry powders.
Effect of thermal and shear stresses in the spray drying process on the stability of siRNA dry powders.
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DOI：
10.1016/j.ijpharm.2019.05.019
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发表时间：
2019-07
影响因子：
5.8
通讯作者：
Jingya Wu;Lan Wu;Feng Wan;J. Rantanen;Dongmei Cun;Mingshi Yang
中科院分区：
文献类型：
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作者：
Jingya Wu;Lan Wu;Feng Wan;J. Rantanen;Dongmei Cun;Mingshi Yang
小干扰 RNA (siRNA) 的肺部递送在治疗基因疾病引起的肺部疾病方面显示出有希望的结果。这项工作的目的是评估喷雾干燥过程中加工引起的热应力和剪切应力对用于吸入的喷雾干燥 siRNA 粉末的固态特性、化学完整性和生物活性的影响。为此，使用实验室规模的喷雾干燥器制备了由EGFP-siRNA和甘露醇组成的可吸入siRNA干粉。使用扫描电子显微镜 (SEM)、激光衍射和 X 射线粉末衍射 (XRPD) 来表征喷雾干燥的 siRNA-甘露醇粉末的固态特性。利用高效液相色谱 (HPLC) 和流式细胞术分别评估 siRNA 制剂的化学稳定性和细胞转染效率。结果表明，随着入口温度的升高，喷雾干燥颗粒由球形变为不规则形状。高入口温度和强雾化条件导致喷雾干燥颗粒中出现更多附聚物。 XRPD分析表明siRNA的存在影响了喷雾干燥粉末中甘露醇的多晶型。随着喷雾干燥过程中热应力和剪切应力的增加，观察到 siRNA 的化学稳定性和细胞转染效率受到损害。与固态的稳定性相比，液态 siRNA 的化学稳定性更容易受到热应力的影响。总之，使用喷雾干燥技术可以生产用于吸入目的的稳定的基于 siRNA 的颗粒。
Pulmonary delivery of small interfering RNAs (siRNAs) has shown promising results for the treatment of lung diseases with gene disorders. The aim of this work was to evaluate the effect of processing-induced thermal and shear stresses during the spray drying process on the solid-state properties, the chemical integrity and the bioactivity of spray-dried siRNA powder intended for inhalation. To this end, inhalable siRNA dry powders composed of EGFP-siRNA and mannitol were prepared by using a lab-scale spray drier. Scanning electron microscopy (SEM), laser diffraction, and X-ray powder diffraction (XRPD) were used to characterize the solid-state properties of the spray-dried siRNA-mannitol powders. High performance liquid chromatography (HPLC) and flow cytometry were exploited to assess the chemical stability and cellular transfection efficiency of siRNA formulations, respectively. The results showed that the spray-dried particles changed from spherical to irregular shape with an increase in the inlet temperature. The high inlet temperature and intensive atomization conditions resulted in more agglomerates in the spray-dried particles. XRPD analysis indicated that the presence of siRNA affected the polymorphic form of mannitol in the spray-dried powder. Compromised chemical stability and cell transfection efficiency of siRNA were observed with an increase in the thermal stress and shear stress during the spray drying process. The chemical stability of siRNA in liquid state was more prone to thermal stress when compared to the stability in the solid-state. In conclusion, stable siRNA based particles for inhalation purposes could be produced using the spray drying technology.