mRNA Center of Excellence, 200 West Street, MA, 02451, Sanofi Waltham, USA.
Translate Bio, Lexington, MA, USA.
Drug Deliv Transl Res. 2024 Feb;14(2):360-372. doi: 10.1007/s13346-023-01402-y. Epub 2023 Aug 1.
Pulmonary delivery of mRNA via inhalation is a very attractive approach for RNA-based therapy for treatment of lung diseases. In this work, we have demonstrated successful development of an mRNA-lipid nanoparticle (LNP) dry powder product (DPP), wherein the LNPs were spray dried using hydroalcoholic solvent along with mannitol and leucine as excipients. The desired critical attributes for the DPP were accomplished by varying the excipients, lipid composition, concentration of LNPs, and weight percentage of mRNA. Leucine alone or in combination with mannitol improved the formulation by increasing the mRNA yield as well as decreasing the particle size. Intratracheal administration of the DPP in mice resulted in luciferase expression in the trachea and lungs indicating successful delivery of functional mRNA. Our results show formulation optimization of mRNA LNPs administered in the form of DPP results in an efficacious functional delivery with great promise for future development of mRNA therapeutics for lung diseases.
通过吸入将 mRNA 递送至肺部是一种非常有吸引力的基于 RNA 的治疗肺部疾病的方法。在这项工作中，我们已经成功地开发了一种 mRNA-脂质纳米颗粒 (LNP) 干粉产品 (DPP)，其中 LNPs 是使用水醇溶剂以及甘露醇和亮氨酸作为赋形剂喷雾干燥的。通过改变赋形剂、脂质组成、LNP 浓度和 mRNA 的重量百分比，可以实现 DPP 的所需关键属性。亮氨酸单独或与甘露醇结合使用可以通过增加 mRNA 的产量和减小粒径来改善配方。在小鼠中通过气管内给予 DPP 导致气管和肺部中的荧光素酶表达，表明功能性 mRNA 的递送达成功。我们的结果表明，以 DPP 形式给予的 mRNA LNP 的配方优化导致有效的功能递送，为未来开发用于肺部疾病的 mRNA 疗法提供了巨大的希望。
