Colloidal stability as a determinant of nanoparticle behavior in the brain
Colloidal stability as a determinant of nanoparticle behavior in the brain
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DOI：
10.1016/j.colsurfb.2018.06.050
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发表时间：
2018-10-01
影响因子：
5.8
通讯作者：
Nance, Elizabeth
中科院分区：
文献类型：
--
作者：
Curtis, Chad;Toghani, Dorsa;Nance, Elizabeth
由于高调节的血脑屏障（BBB）和复杂的脑微环境，药物递送到大脑是具有挑战性的。纳米颗粒，由于其可定制性，提供了有前途的平台，以加强治疗递送，实现控制释放和疾病特异性定位在大脑中。然而，我们还没有完全理解纳米粒子和它们所处的生物环境之间复杂的相互作用。重要的是要进行系统的研究，以表征纳米颗粒的行为作为脑脊液（CSF）中离子组成、浓度和pH值的函数。这些可以改变纳米颗粒的生物学特性，影响扩散能力和细胞摄取。本研究利用聚乙二醇（PEG）包覆和羧基包覆聚苯乙烯（PS-PEG和PS-COOH）纳米粒子（NPs）在脑微环境相关条件下的聚集动力学、胶体稳定性和扩散能力进行了研究。尺寸、表面电荷和表面涂层在CSF离子浓度和组成、pH条件和温度范围内发生变化。钙浓度和pH值的微小变化会使脑脊液中的纳米颗粒不稳定。然而，与PS-COOH NPs相比，PS-PEG NPs在更广泛的条件下保持稳定，并且在琼脂糖凝胶、体外脑微环境模型和器官型脑组织切片模型中具有更高的扩散能力。这些结果表明，在广泛的条件下，需要空间稳定来保持纳米颗粒的胶体稳定性。重要的是，胶体稳定允许增加扩散能力，并可用于预测大脑微环境中的扩散行为。
Drug delivery to the brain is challenging due to a highly regulated blood-brain barrier (BBB) and a complex brain microenvironment. Nanoparticles, due to their tailorability, provide promising platforms to enhance therapeutic delivery and achieve controlled release and disease-specific localization in the brain. However, we have yet to fully understand the complex interactions between nanoparticles and the biological environments in which they operate. It is important to perform a systematic study to characterize nanoparticle behavior as a function of ion composition, concentration, and pH in cerebrospinal fluid (CSF). These could alter nanoparticle biological identity and influence diffusive capability and cellular uptake. In this study, poly(ethylene glycol) (PEG)-coated and carboxyl-coated polystyrene (PS-PEG and PS-COOH respectively) nanoparticles (NPs) were used to evaluate the aggregation kinetics, colloidal stability, and diffusive capability of nanoparticles in conditions relevant to the brain microenvironment. Size, surface charge, and surface coating were varied in a range of CSF ion concentrations and compositions, pH conditions, and temperatures. Small changes in calcium concentration and pH destabilize nanoparticles in CSF. However, PS-PEG NPs remain stable over a wider variety of conditions than PS-COOH NPs, and have higher diffusion capabilities in both agarose gels, an in vitro model of the brain microenvironment, and an organotypic brain tissue slice model. These results demonstrate the need for steric stabilization to maintain nanoparticle colloidal stability in a wide range of conditions. Importantly, colloidal stabilization allows for increased diffusive capability and can be used to predict diffusive behavior in the brain microenvironment.