Liu Yingying, Shen Hua, Zang Hengchang, Shi Yanbin, Qiu Shengnan, Fu Xianglei, Zhang Yankun, Chen Xiangqin, Zhou Jiamin, Wan Xiaoyu, Lin Guimei
School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.
J Pharm Sci. 2025 Feb;114(2):1455-1463. doi: 10.1016/j.xphs.2024.12.023. Epub 2024 Dec 24.
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.
为延缓类风湿性关节炎（RA）患者病情进展，并通过在炎症早期进行药物干预预防进一步的致畸作用和不可逆的骨质侵蚀，本实验以编码热休克蛋白10（HSP10）的信使核糖核酸（H-mRNA）作为主要治疗药物，利用微流控技术制备含H-mRNA的脂质纳米颗粒（LNP）（H-mRNA LNPs），并使用肝素颗粒修饰H-mRNA-LNPs表面，得到最终制剂H-mRNA-LNPs@肝素/鱼精蛋白。通过对H-mRNA的序列改造及效果评估，探究了所制备脂质纳米颗粒的制剂筛选、物理表征、体外细胞毒性、体内分布、体内药效学及体内安全性，证明该纳米制剂具有良好的抗类风湿性关节炎作用，并对核酸药物在肿瘤以外疾病治疗中的应用进行了初步探索。本研究将为RA的治疗提供新思路。
