空军军医大学学报2024，Vol.45Issue(1)：73-79,7.DOI:10.13276/j.issn.2097-1656.2024.01.015
2-脱氧葡萄糖修饰共载siPD-L1及替莫唑胺脂质纳米粒的脑靶向性研究
Brain targeting of 2-deoxyglucose modified lipid nanoparticles co-loaded with siPD-L1 and temozolomide
摘要
Abstract
Objective To investigate the pharmacokinetics and brain distribution of 2-deoxyglucose(2-DG)modified lipid nanoparticles co-loaded siPD-L1 and temozolomide(TMZ)(TMZ/siPD-L1@GLPN)in mice,and to clarify the brain targeting of TMZ/siPD-L1@GLPN,so as to provide a basis for the design of brain targeted drug delivery system.Methods High performance liquid chromatography and in vivo imager were used to study the elimination kinetics of TMZ in plasma and the distribution kinetics of TMZ in the brain of mice after the administration of free TMZ,TMZ/siPD-L1@GLPN and TMZ/siPD-L1@LPN via tail vein injection.Results Compared with free TMZ,the elimination rate of TMZ/siPD-L1@GLPN in mouse plasma was significantly slowed down,and the circulation time of TMZ/siPD-L1@GLPN in mice was significantly prolonged.After the administration of free TMZ,TMZ/siPD-L1@GLPN and TMZ/siPD-L1@LPN,the AUC0-∞ of TMZ in plasma were(139.49±14.39),(585.50±44.91)and(705.73±173.02)h/(mg·L),respectively.The AUC0-∞ of TMZ in brain tissue were(32.39±3.12),(532.89±46.44)and(162.79±18.38)h/(mg·kg),respectively.The results of in vivo imager observation showed that TMZ/siPD-L1@GLPN was more distributed in the brain than TMZ/siPD-L1@LPN.Conclusion 2-DG modified lipid nanoparticles can significantly improve the brain targeting of lipid nanoparticles,and significantly prolong the circulation time of TMZ in mice.关键词
替莫唑胺/药代动力学/脑胶质瘤/高效液相色谱/活体成像Key words
temozolomide/pharmacokinetics/glioma/high performance liquid chromatography/in vivo imager分类
医药卫生引用本文复制引用
罗静远,杨静,李雪,周四元,刘道洲..2-脱氧葡萄糖修饰共载siPD-L1及替莫唑胺脂质纳米粒的脑靶向性研究[J].空军军医大学学报,2024,45(1):73-79,7.基金项目
陕西省重点研发计划一般项目(2023-YBSF-221) （2023-YBSF-221）
