Department of Chemical Engineering, University of Washington, 98195, Seattle, WA, USA.
Department of Chemical Engineering, University of Washington, 98195, Seattle, WA, USA; Department of Biochemistry, University of Washington, 98195, Seattle, WA, USA.
Biomaterials. 2021 Oct;277:121086. doi: 10.1016/j.biomaterials.2021.121086. Epub 2021 Aug 28.
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.
药物递送至脑部受到血脑屏障（BBB）、脑实质内以及进入特定靶细胞的通透性差的限制。纳米技术可以克服这些障碍，但它的这种能力取决于纳米颗粒的物理化学特性，包括表面化学。表面化学可以由许多因素决定，包括在制剂过程中引入的稳定表面活性剂分子的存在。用泊洛沙姆 188（F68）、泊洛沙姆 407（F127）和聚山梨酯 80（P80）包被的纳米颗粒已被证明能被 BBB 内皮细胞摄取，并增强在脑内的积累。然而，为了设计能够有效克服脑部药物递送障碍的纳米疗法，必须更好地了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。在这里，我们评估了生物相容性且常用的表面活性剂胆酸（CHA）、F68、F127、P80 和聚乙烯醇（PVA）对聚乳酸-聚乙二醇（PLGA-PEG）纳米颗粒向脑部和脑部内转运的影响。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，这反映了表面活性剂在短距离和短时间尺度上促进细胞相互作用的作用。在体内给药后，PLGA-PEG/P80 纳米颗粒显示出增强的 BBB 穿透能力，随后在神经元和小胶质细胞内内化。因此，将表面活性剂纳入 PLGA-PEG 纳米颗粒的制剂中是控制纳米颗粒在脑内命运的一个重要设计参数。
