最多等待 10 秒，若超时请稍后重试。
Åsa Sandelius, Humaira Naseer, Johnny Lindqvist, Amanda Wilson, Neil Henderson
Integrated Bioanalysis, Clinical Pharmacology & Safety Sciences, BioPharmaceutical R&D, AstraZeneca, Pepparredsleden 1, Mölndal, SE 43183, Sweden.
Integrated Bioanalysis, Clinical Pharmacology & Safety Sciences, BioPharmaceutical R&D, AstraZeneca, Cambridge Biomedical Campus, 1 Francis Crick Avenue, Cambridge, CB2 0AA, UK.
Bioanalysis. 2024;16(14):721-733. doi: 10.1080/17576180.2024.2360361. Epub 2024 Jun 28.
Increased knowledge of biodistribution and pharmacokinetics of lipid nanoparticle (LNP)-encapsulated mRNA drug components may aid efficacy and safety evaluation. 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. 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. Subcutaneously dosing LNP encapsulated mRNA in mice resulted in a nonlinear relationship of LNP, mRNA and protein concentration across multiple tissues.
增加对脂质纳米颗粒（LNP）包裹的 mRNA 药物成分的生物分布和药代动力学的了解可能有助于评估疗效和安全性。将 LNP 包裹的增强型绿色荧光蛋白 mRNA 皮下给予小鼠，并在给药后长达 72 小时取样。通过 LC-MS、分支 DNA 和 ELISA 定量测定 LNP、mRNA 和翻译蛋白。LNP 和 mRNA 的最高水平在皮肤和脾脏中检测到，其次是脾脏，但也迅速分布到循环系统中。翻译蛋白在皮肤和脾脏中显示出高浓度，但在肝脏和肾脏中也在 24 小时内 LNP 在 4 小时内清除。在小鼠中皮下给予 LNP 包裹的 mRNA 导致 LNP、mRNA 和蛋白质浓度在多个组织中的非线性关系。
