Abstract：
Aim: Increased knowledge of biodistribution and pharmacokinetics of lipid nanoparticle (LNP)-encapsulated mRNA drug components may aid efficacy and safety evaluation. Methods: Mice were subcutaneously administrated LNP encapsulated enhanced green fluorescent protein mRNA and sampled up to 72 h after dosing. LNP, mRNA and translated protein were quantified by LC-MS, branched DNA and ELISA. Results: Highest levels of LNP and mRNA were detected in skin, followed by spleen, but also rapidly distributed to circulation. Translated protein showed high concentration in skin and spleen, but also in liver and kidney across 24 h where the LNP was cleared at 4 h. Conclusion: Subcutaneously dosing LNP encapsulated mRNA in mice resulted in a nonlinear relationship of LNP, mRNA and protein concentration across multiple tissues.
[Box: see text].
[Box: see text].
摘要：
目的：增加脂质纳米颗粒（LNP）包裹的mRNA药物成分的生物分布和药代动力学的知识可能有助于疗效和安全性评估。方法：小鼠皮下给药LNP包裹的增强型绿色荧光蛋白mRNA，并在给药后72小时取样。LNP,通过LC-MS定量mRNA和翻译蛋白，分支DNA和ELISA。结果：在皮肤中检测到最高水平的LNP和mRNA，接着是脾脏,而且还迅速分配到流通中。翻译蛋白在皮肤和脾脏中呈高浓度，而且在肝脏和肾脏中，LNP在4小时被清除。结论：皮下给药LNP在小鼠中封装的mRNA导致LNP的非线性关系，跨多个组织的mRNA和蛋白质浓度。
[方框：见正文]。
[方框：见正文]。
