乳铁蛋白和转铁蛋白偶联聚合物囊泡在脑靶向中的作用：体外和体内评价。
Effect of lactoferrin- and transferrin-conjugated polymersomes in brain targeting: in vitro and in vivo evaluations.
机构信息
Department of Pharmaceutics, Fudan University, Shanghai, China.
出版信息
Acta Pharmacol Sin. 2010 Feb;31(2):237-43. doi: 10.1038/aps.2009.199.
AIM
To evaluate the effect of lactoferrin (Lf) and transferrin (Tf) in brain targeting.
METHODS
Polymersomes (PSs), employed as vectors, were conjugated with Lf or Tf and were characterized by morphology, particle size, zeta potential, and surface densities of the Lf or Tf molecules. In vitro uptake of Lf-PS and Tf-PS by bEnd.3 cells was investigated using coumarin-6 as a fluorescent probe. In vivo tissue distribution and pharmacokinetics of (125)I-Lf-PS and (125)I-Tf-PS were also examined.
RESULTS
The mean particle size of PS, Lf-PS, and Tf-PS was around 150 nm and the zeta potential of the PSs was about -20 mV. Less than 0.12% of the coumarin was released from coumarin-6-loaded PS in 84 h indicating that coumarin-6 was an accurate probe for the PSs' behavior in vitro. It was shown that the uptake of Lf-PS and Tf-PS by bEnd.3 cells was time-, temperature-, and concentration-dependent. Both Lf and Tf could increase the cell uptake of PSs at 37 degrees C, but the uptake of Tf-PS was significantly greater than that of Lf-PS. In vivo tissue distribution and pharmacokinetics in mice revealed higher brain uptake and distribution of Tf-PS than Lf-PS, which was in accordance with in vitro uptake results. The drug targeting index (DTI) of Tf-PS with regard to Lf-PS was 1.51.
CONCLUSION
Using a PS as the delivery vector and bEnd.3 cells as the model of the blood-brain barrier (BBB), Tf was more effective than Lf in brain targeting.
目的
评估乳铁蛋白（Lf）和转铁蛋白（Tf）在脑部靶向中的作用。
方法
采用聚合物囊泡（PSs）作为载体，通过形态、粒径、Zeta 电位和 Lf 或 Tf 分子的表面密度对其进行表征。采用香豆素-6 作为荧光探针，研究 bEnd.3 细胞对 Lf-PS 和 Tf-PS 的体外摄取。还研究了（125）I-Lf-PS 和（125）I-Tf-PS 的体内组织分布和药代动力学。
结果
PS、Lf-PS 和 Tf-PS 的平均粒径约为 150nm，PSs 的 Zeta 电位约为-20mV。在 84 小时内，从载有香豆素的 PS 中释放的香豆素少于 0.12%，表明香豆素-6 是 PS 体外行为的准确探针。结果表明，bEnd.3 细胞对 Lf-PS 和 Tf-PS 的摄取与时间、温度和浓度有关。在 37°C 时，Lf 和 Tf 均可增加 PSs 的细胞摄取，但 Tf-PS 的摄取明显大于 Lf-PS。在小鼠体内组织分布和药代动力学研究中，Tf-PS 对 Lf-PS 的脑摄取和分布更高，这与体外摄取结果一致。Tf-PS 的药物靶向指数（DTI）相对于 Lf-PS 为 1.51。
结论
使用 PS 作为递送载体，bEnd.3 细胞作为血脑屏障（BBB）的模型，Tf 比 Lf 更有效地靶向脑部。
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