Brain targeting of 2-deoxyglucose modified lipid nanoparticles co-loaded with siPD-L1 and temozolomide
LUO Jingyuan
YANG Jing
LI Xue
ZHOU Siyuan
LIU Daozhou
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.
Keywords：temozolomidepharmacokineticsgliomahigh performance liquid chromatographyin vivo imager
Publication Date：2024-01-28
Online Publishing Date：2026-08-26(First online date of this platform, not the publication date of the document)
Pages：7( 73-79 )