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Transcellular Model for Neutral and Charged Nanoparticles Across an In Vitro Blood–Brain Barrier
Cardiovascular Engineering and Technology ( IF 1.8 ) Pub Date : 2020-10-28 , DOI: 10.1007/s13239-020-00496-6
Lin Zhang 1 , Jie Fan 1 , Guanglei Li 1 , Zhaokai Yin 1 , Bingmei M Fu 1
Affiliation  

Purpose

The therapeutic drug-loaded nanoparticles (NPs, 20–100 nm) have been widely used to treat brain disorders. To improve systemic brain delivery efficacy of these NPs, it is necessary to quantify their transport parameters across the blood–brain barrier (BBB) and understand the underlying transport mechanism.

Methods

Permeability of an in vitro BBB, bEnd3 (mouse brain microvascular endothelial cells) monolayer, to three neutral NPs with the representative diameters was measured using an automated fluorometer system. To elucidate the transport mechanism of the neutral NPs across the in vitro BBB, and that of positively charged NPs whose BBB permeability was measured in a previous study, we developed a novel transcellular model, which incorporates the charge of the in vitro BBB, the mechanical property of the cell membrane, the ion concentrations of the surrounding salt solution and the size and charge of the NPs.

Results

Our model indicates that the negative charge of the surface glycocalyx and basement membrane of the BBB plays a pivotal role in the transcelluar transport of NPs with diameter 20-100 nm across the BBB. The electrostatic force between the negative charge at the in vitro BBB and the positive charge at NPs greatly enhances NP permeability. The predictions from our transcellular model fit very well with the measured BBB permeability for both neutral and charged NPs.

Conclusion

Our model can be used to predict the optimal size and charge of the NPs and the optimal charge of the BBB for an optimal systemic drug delivery strategy to the brain.



中文翻译:

跨越体外血脑屏障的中性和带电纳米粒子的跨细胞模型

目的

治疗性载药纳米粒子(NP,20-100 nm)已广泛用于治疗脑部疾病。为了提高这些 NPs 的系统性脑传递效率,有必要量化它们穿过血脑屏障 (BBB) 的转运参数并了解潜在的转运机制。

方法

使用自动荧光计系统测量了体外BBB、bEnd3(小鼠脑微血管内皮细胞)单层对具有代表性直径的三个中性 NP 的渗透性。为了阐明中性 NPs在体外BBB 中的转运机制,以及在先前研究中测量 BBB 通透性的带正电 NPs 的转运机制,我们开发了一种新的跨细胞模型,该模型结合了体外BBB 的电荷、机械细胞膜的性质、周围盐溶液的离子浓度以及纳米粒子的大小和电荷。

结果

我们的模型表明,BBB 表面糖萼和基底膜的负电荷在直径为 20-100 nm 的 NP 跨 BBB 的跨细胞转运中起关键作用。体外BBB处的负电荷与 NPs 处的正电荷之间的静电力大大提高了 NP 的渗透性。我们的跨细胞模型的预测与测量的中性和带电 NP 的 BBB 渗透性非常吻合。

结论

我们的模型可用于预测 NP 的最佳大小和电荷以及 BBB 的最佳电荷,以实现向大脑的最佳全身药物递送策略。

更新日期:2020-10-30
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