Drug delivery to the brain is limited by poor penetration of pharmaceutical agents across the blood-brain barrier (BBB), within the brain parenchyma, and into specific cells of interest. Nanotechnology can overcome these barriers, but its ability to do so is dependent on nanoparticle physicochemical properties including surface chemistry. Surface chemistry can be determined by a number of factors, including by the presence of stabilizing surfactant molecules introduced during the formulation process. Nanoparticles coated with poloxamer 188 (F68), poloxamer 407 (F127), and polysorbate 80 (P80) have demonstrated uptake in BBB endothelial cells and enhanced accumulation within the brain. However, the impact of surfactants on nanoparticle fate, and specifically on brain extracellular diffusion or intracellular targeting, must be better understood to design nanotherapeutics to efficiently overcome drug delivery barriers in the brain. Here, we evaluated the effect of the biocompatible and commonly used surfactants cholic acid (CHA), F68, F127, P80, and poly (vinyl alcohol) (PVA) on poly (lactic-co-glycolic acid)-poly (ethylene glycol) (PLGA-PEG) nanoparticle transport to and within the brain. The inclusion of these surfactant molecules decreases diffusive ability through brain tissue, reflecting the surfactant's role in encouraging cellular interaction at short length and time scales. After in vivo administration, PLGA-PEG/P80 nanoparticles demonstrated enhanced penetration across the BBB and subsequent internalization within neurons and microglia. Surfactants incorporated into the formulation of PLGA-PEG nanoparticles therefore represent an important design parameter for controlling nanoparticle fate within the brain.

药物通过血脑屏障 (BBB)、脑实质和特定目标细胞的渗透性差，限制了向大脑的药物输送。纳米技术可以克服这些障碍，但其能力取决于纳米粒子的物理化学性质，包括表面化学。表面化学可以由许多因素决定，包括稳定表面活性剂的存在在配方过程中引入的分子。涂有泊洛沙姆 188 (F68)、泊洛沙姆 407 (F127) 和聚山梨醇酯 80 (P80) 的纳米颗粒已证明可被 BBB 内皮细胞吸收并增强脑内的积累。然而，必须更好地理解表面活性剂对纳米颗粒命运的影响，特别是对脑细胞外扩散或细胞内靶向的影响，以设计纳米治疗药物以有效克服大脑中的药物输送障碍。在这里，我们评估了生物相容性和常用表面活性剂胆酸 (CHA)、F68、F127、 P80和聚乙烯醇 (PVA) 对聚 (乳酸) 的影响。-乙醇酸）-聚（乙二醇）（PLGA-PEG）纳米颗粒转运到大脑和大脑内。这些表面活性剂分子的加入降低了通过脑组织的扩散能力，反映了表面活性剂在促进短时间和短时间尺度内细胞相互作用方面的作用。在体内给药后，PLGA-PEG/P80 纳米粒子表现出增强的穿过 BBB 的渗透以及随后在神经元和小胶质细胞内的内化。因此，掺入 PLGA-PEG 纳米粒子配方中的表面活性剂代表了控制大脑内纳米粒子命运的重要设计参数。