Song Yang, Cai Xiaoli, Du Dan, Dutta Prashanta, Lin Yuehe
School of Mechanical and Material Engineering, Washington State University, Pullman, Washington 99164, United States.
ACS Appl Bio Mater. 2019 Mar 18;2(3):1050-1055. doi: 10.1021/acsabm.8b00654. Epub 2019 Jan 25.
Different types of blood-brain barrier (BBB) models have been constructed and applied for drug transport to evaluate the efficacy of nano-carrier based drug delivery. However, the effectiveness of different types of BBB models has not been reported. In this paper, we developed two types of models: one-cell type BBB model developed using only endothelial cells and three-cell type BBB model obtained by co-culturing endothelial, pericyte and astrocyte cells. The nanoparticle transport mechanisms through BBB and transport efficiencies of the Lactoferrin attached silica nanoparticles were studied using both types of the BBB models. Compared with one-cell type model, the PSi-Lf NPs exhibit relatively lower transport efficiency across three-cell type BBB system. Moreover, the effects of the nanoparticle size on the transport efficacies are consistent for both models. For both types of BBB models, the transport efficacies of the NPs are size dependent, and the highest efficacies are achieved for NPs with 25 nm in diameter. Our experimental results indicate that the one-cell type and three-cell type BBB models are equivalent for evaluating and optimizing nanoparticle transport across BBB.
已经构建了不同类型的血脑屏障(BBB)模型,并将其应用于药物转运,以评估基于纳米载体的药物递送效果。然而,不同类型BBB模型的有效性尚未见报道。在本文中,我们开发了两种模型:仅使用内皮细胞构建的单细胞型BBB模型,以及通过共培养内皮细胞、周细胞和星形胶质细胞获得的三细胞型BBB模型。使用这两种类型的BBB模型研究了纳米颗粒通过血脑屏障的转运机制以及乳铁蛋白附着的二氧化硅纳米颗粒的转运效率。与单细胞型模型相比,PSi-Lf NPs在三细胞型BBB系统中的转运效率相对较低。此外,纳米颗粒大小对两种模型的转运效率的影响是一致的。对于两种类型的BBB模型,纳米颗粒的转运效率均取决于颗粒大小,直径为25 nm的纳米颗粒转运效率最高。我们的实验结果表明,单细胞型和三细胞型BBB模型在评估和优化纳米颗粒通过血脑屏障的转运方面是等效的。