中国兽医杂志2025，Vol.61Issue(4)：1-10,10.DOI:10.20157/j.cnki.zgsyzz.2025.04.001
转铁蛋白修饰的辣蓼黄酮脂质体的药代动力学和脑靶向性研究
Pharmacokinetic and Brain Targeting Study of Transferrin-Modified Polygonum hydropiper L.Flavonoid Liposomes
摘要
Abstract
To investigate the pharmacokinetic characteristics of transferrin(Tf)-modified flavonoid of Polygonum hydropiper L.(FPHL)liposomes(Tf-FPHL-Lip)and to clarify the effect of Tf modification on liposome permeability across the blood-brain barrier(BBB)both in vitro and in vivo,this study established a high-performance liquid chromatography(HPLC)method for the determination of rutin concentration in rat plasma and analyzed the pharmacokinetics of Tf-FPHL-Lip in rats.An in vitro BBB model was constructed using mouse brain microvascular endothelial cells(bEnd3)and cerebellar astrocytes(C8-D1A)to evaluate the permeability of Lip across the BBB.Additionally,Tf-FPHL-Lip was administered to mice via tail vein injection,and the distribution of fluorescently labeled Lip in vivo was observed using small animal live imaging technology to assess the BBB permeability of Tf-FPHL-Lip in vivo.The results demonstrated that the established HPLC method met the requirements for pharmacokinetic analysis in terms of specificity,linearity,recovery,and precision.Compared wtih the FPHL group,both FPHL-Lip and Tf-FPHL-Lip groups exhibited significantly increased peak plasma concentration(Cmax),area under the plasma drug concentration-time curve from 0 to infinity(AUC0-∞),area under the plasma drug concentration-time curve from time 0 to time t(AUC0-t),mean residence time(MRT0-∞),and half-life(T1/2)(P<0.01),while clearance(CL)was significantly reduced(P<0.01).The Cmax,AUC0-∞,AUC0-t,MRT0-∞,and T1/2 of the Tf-FPHL-Lip group were 1.12,1.17,1.16,1.01,and 1.03 times those of the FPHL-Lip group,respectively.The peak area under the plasma drug concentration-time curve was highest in the Tf-FPHL-Lip group and lowest in the FPHL group.In the Transwell assay,the fluorescence signal intensity in the lower chamber of the Tf-modified Rhodamine B(Tf-RhB-Lip)group was significantly higher than that of the Rhodamine B liposome(RhB-Lip)group(P<0.01),indicating enhanced BBB penetration in vitro following Tf modification.Similarly,in the in vivo imaging experiment,the fluorescence signal intensity in the brain of the Tf-modified indocyanine green(ICG)liposome(Tf-ICG-Lip)group was significantly higher than that of the ICG liposome(ICG-Lip)and ICG groups(P<0.01),with fluorescence persisting for up to 36 hours,indicating that Tf modification enhances the BBB permeability of Lip in vivo.In conclusion,Tf modification promotes the penetration of liposomal drugs through both in vitro and in vivo BBB models,increases drug absorption,and provides a sustained-release effect for Tf-FPHL-Lip.These findings provide a theoretical basis for the brain-targeted delivery of Tf-FPHL-Lip and offer valuable insights for clinical drug applications.关键词
转铁蛋白/辣蓼黄酮/脂质体/药代动力学/血脑屏障Key words
transferrin/flavonoid of Polygonum hydropiper L./liposome/pharmacokinetic/blood-brain barrier分类
畜牧业引用本文复制引用
吴昌旭,于美玲,张金武,彭春子,吕茂杰,杨世森,韦英益,陈海兰,何家康,胡庭俊..转铁蛋白修饰的辣蓼黄酮脂质体的药代动力学和脑靶向性研究[J].中国兽医杂志,2025,61(4):1-10,10.基金项目
国家自然科学基金项目(32202850,32360894) （32202850,32360894）
广西自然科学基金面上基金项目(2021GXNSFAA196004) （2021GXNSFAA196004）
广西大学自然科学与技术创新发展倍增计划项目(2024BZRC013) （2024BZRC013）
