Surfactants influence polymer nanoparticle fate within the brain.
Surfactants influence polymer nanoparticle fate within the brain.
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DOI：
10.1016/j.biomaterials.2021.121086
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发表时间：
2021-10
期刊：
影响因子：
14
通讯作者：
Nance E
中科院分区：
文献类型：
--
作者：
Joseph A;Simo GM;Gao T;Alhindi N;Xu N;Graham DJ;Gamble LJ;Nance E
药物递送至脑受到药剂穿过血脑屏障（BBB）、在脑实质内以及进入感兴趣的特定细胞的不良渗透的限制。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。表面化学可由许多因素决定，包括在配制过程中引入的稳定表面活性剂分子的存在。已证明用泊洛沙姆188（F68）、泊洛沙姆407（F127）和聚山梨酯80（P80）包被的纳米颗粒在BBB内皮细胞中的摄取和在脑内的增强的蓄积。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，以设计纳米治疗剂，从而有效地克服脑中的药物递送障碍。在这里，我们评估了生物相容性和常用的表面活性剂胆酸（CHA），F68，F127，P80和聚（乙烯醇）（PVA）对聚（乳酸-共-乙醇酸）-聚（乙二醇）（PLGA-PEG）纳米颗粒运输到大脑和在大脑内的影响。包含这些表面活性剂分子降低了通过脑组织的扩散能力，反映了表面活性剂在短长度和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纳米颗粒制剂中的表面活性剂代表了用于控制脑内纳米颗粒命运的重要设计参数。
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.
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影响因子：
17.1
作者：
Hutter, Eliza;Boridy, Sebastien;Maysinger, Dusica
通讯作者：
Maysinger, Dusica
影响因子：
4.3
作者：
Hering, Indra;Eilebrecht, Elke;Wacker, Matthias G.
通讯作者：
Wacker, Matthias G.
影响因子：
14
作者：
ILLUM, L;JACOBSEN, LO;DAVIS, SS
通讯作者：
DAVIS, SS
影响因子：
9.7
作者：
Jain, Atul;Jain, Ashay;Soni, Vandana
通讯作者：
Soni, Vandana
影响因子：
5.6
作者：
Liao, Rick;Wood, Thomas R.;Nance, Elizabeth
通讯作者：
Nance, Elizabeth