A Study on the Treatment of Rheumatoid Arthritis with Lipid Nanoparticles Containing mRNA encoding Heat shock protein 10

• Published in: Journal of pharmaceutical sciences 2024-12
• Main Authors: Liu, Yingying, Shen, Hua, Zang, Hengchang, Shi, Yanbin, Qiu, Shengnan, Fu, Xianglei, Zhang, Yankun, Chen, Xiangqin, Zhou, Jiamin, Wan, Xiaoyu, Lin, Guimei
• Format: Article
• Language: English
• Subjects: Lipid nanoparticles; Messenger RNA (mRNA); Microfluidic technology; Rheumatoid arthritis (RA)
• ISSN: 0022-3549; 1520-6017; 1520-6017
• DOI: 10.1016/j.xphs.2024.12.023

In order to delay the progression of Rheumatoid Arthritis (RA) in patients, and to prevent further teratogenesis and irreversible bone erosion through drug intervention in the early stages of inflammation, this experiment used the mRNA encoding heat shock protein 10 (HSP10) (H-mRNA) as the main therapeutic drug and used Microfluidics technology to prepare lipid nanoparticles (LNP) (H-mRNA LNPs) containing H-mRNA, and the surface of H-mRNA-LNPs was modified using heparin particals to obtain the final formulation H-mRNA-LNPs @ heparin/ Protamine. Through the sequence modification and effect evaluation of H-mRNA, we explored the formulation screening, physical characterization, cytotoxicity in vitro, distribution in vivo, pharmacodynamics in vivo, and safety in vivo of the prepared lipid nanoparticles, which proved that this nano-preparation had good anti Rheumatoid Arthritis effects, and conducted a preliminary exploration for the application of nucleic acid drugs in the treatment of diseases outside of tumors. This research would provide new ideas for the treatment of RA. Schematic diagram of mRNA loaded LNP and HLH acting through systemic administration [Display omitted]