Department of Drug Delivery Research, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan.
Department of Drug Delivery Research, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan.
J Pharm Sci. 2019 Aug;108(8):2661-2667. doi: 10.1016/j.xphs.2019.03.029. Epub 2019 Apr 5.
In order to evaluate the in vivo effect of inhaled formulations, it is a gold standard to create a lung metastasis model by intravenously injecting cancer cells into an animal. Because the cancer grows from the blood vessel side, there is a possibility of underestimating the effect of an inhaled formulation administered to the lung epithelium side. In addition, the metastasis model has disadvantages in terms of preparation time and expense. The present study aimed to establish a new method to evaluate the effect of an inhaled small interfering RNA (siRNA) formulation that is more correct, more rapid, and less expensive. We investigated whether siRNA can suppress gene expression of plasmid DNA (pDNA) by serial pulmonary administration of siRNA and pDNA powders prepared by spray-freeze-drying. We revealed that formulations of dry siRNA powder significantly suppressed gene expression of pDNA powder compared with a control group with no siRNA. Naked siRNA inhalation powder with no vector showed the suppression of gene expression equivalent to that of an siRNA-polyethyleneimine complex without damaging tissues. These results show that the present method is suitable for evaluating the gene-silencing effect of inhaled siRNA powders.
为了评估吸入制剂的体内效果，通过将癌细胞静脉注射到动物体内来创建肺转移模型是金标准。因为癌症从血管侧生长，所以有可能低估施用于肺上皮侧的吸入制剂的效果。此外，转移模型在制备时间和费用方面存在缺点。本研究旨在建立一种更正确、更快速、更经济的评估吸入小干扰 RNA(siRNA)制剂效果的新方法。我们研究了通过连续肺部给予 siRNA 和通过喷雾冷冻干燥制备的 pDNA 粉末，siRNA 是否可以抑制质粒 DNA(pDNA)的基因表达。我们揭示了与没有 siRNA 的对照组相比，干燥的 siRNA 粉末制剂显著抑制了 pDNA 粉末的基因表达。没有载体的裸露 siRNA 吸入粉末显示出与不损伤组织的 siRNA-聚亚乙基亚胺复合物相当的基因表达抑制。这些结果表明，本方法适用于评估吸入 siRNA 粉末的基因沉默效果。
