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吸入式干粉用于肺部mRNA输送

Akiva Gordon^1,2, Bowen Li^1,2,3,4,5, Jacob Witten^1,2,6

¹David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.

Advanced healthcare materials

|October 1, 2024

概括

使用喷雾冷干燥开发可吸入的mRNA干粉是一种安全有效的肺部输送方法. 这些稳定,强效的配方通过吸入使mRNA有效地分布到深肺.

科学领域:

生物技术是生物技术.
肺部药物输送肺部药物输送
纳米医学是一种纳米医学.

背景情况:

使者RNA (mRNA) 疗法显示出希望,但在肺部传递方面面临挑战.
液态mRNA配方的直接内灌注在人类中引发了安全和分发方面的担忧.
吸入式配方是安全有效的mRNA输送到肺部的必要条件.

研究的目的:

开发稳定,可吸入的脂质纳米颗粒干粉配方,用于将mRNA输送到肺部.
为了评估这些干粉配方的气溶性质和肺mRNA输送效率.
评估开发的配方与各种电离性脂质的兼容性.

主要方法:

喷雾冷干燥被用来创建干粉脂质纳米粒子配方.
气溶性质的特征是通过测量平均质量空气动力直径 (MMAD) 和微粒分数 (FPF) 来进行.
在体内肺部mRNA输送被评估为不同的可电离脂基配方.

主要成果:

干粉配方表现出适合深肺输送的气溶性质 (MMAD 3-4微米,FPF ≈40%).
四种不同的基于可电离脂的配方已成功制备为可吸入的干粉.
所有评估的干粉配方在体内证明肺mRNA输送与液体配方相比.

结论:

喷雾冷干燥的脂质纳米颗粒干粉是可吸入mRNA治疗的有希望的平台.
开发的配方是强大的,生物活性,并与各种电离性脂质兼容.
这项工作为吸入mRNA干粉治疗肺部疾病的临床开发铺平了道路.

关键词:

干粉是干的干粉是干的脂质纳米颗粒的使用方法提供mRNA的交付.肺部输送是通过肺部进行的.

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