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首页> 外文期刊>The European Journal of Neuroscience >Quantification and localization of PEGylated polycyanoacrylate nanoparticles in brain and spinal cord during experimental allergic encephalomyelitis in the rat.
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Quantification and localization of PEGylated polycyanoacrylate nanoparticles in brain and spinal cord during experimental allergic encephalomyelitis in the rat.

机译：在实验性变应性脑脊髓炎大鼠中，聚乙二醇化聚氰基丙烯酸酯纳米颗粒在大脑和脊髓中的定量和定位。

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摘要

Under healthy conditions, the blood-brain barrier (BBB) limits the passage of solutes and cells from the blood to the CNS. During neurological diseases, BBB permeability increases dramatically and it has been hypothesized that drug carrier systems such as polymeric nanoparticles could cross the BBB and penetrate into the CNS. PEGylated polyalkylcyanoacrylate nanoparticles (long-circulating carrier) are one such system and have been investigated during experimental allergic encephalomyelitis (EAE). Brain and spinal cord concentrations of [(14)C]-radiolabelled PEGylated polyalkylcyanoacrylate nanoparticles were compared with another blood long-circulating carrier (poloxamine 908-coated polyalkylcyanoacrylate nanoparticles) and with conventional non-long-circulating polyalkylcyanoacrylate nanoparticles. The microscopic localization of fluorescent nanoparticles in the CNS was also investigated in order to further understand the mechanism by which the particles penetrate the BBB. The results demonstrate that the concentration of PEGylated nanoparticles in the CNS, especially in white matter, is greatly increased in comparison to conventional non-PEGylated nanoparticles. In addition, this increase was significantly higher in pathological situations where BBB permeability is augmented and/or macrophages have infiltrated. Passive diffusion and macrophage uptake in inflammatory lesions seems to be the mechanism underlying such particles' brain penetration. Based on their long-circulating properties in blood and on their surface characteristics that allow cell interactions, PEGylated nanoparticles penetrated into CNS to a larger extent than all the other formulations tested. Thus, PEGylated polycyanoacrylate nanoparticles are proposed here as a new brain delivery system for neuroinflammatory diseases.
机译：在健康条件下，血脑屏障（BBB）限制了溶质和细胞从血液到中枢神经系统的通道。在神经系统疾病期间，血脑屏障通透性急剧增加，并且已经假设药物载体系统（例如聚合物纳米粒子）可以穿过血脑屏障并渗入中枢神经系统。聚乙二醇化聚氰基丙烯酸烷基酯纳米颗粒（长循环载体）就是这样一种系统，并已在实验性变应性脑脊髓炎（EAE）中进行了研究。将[（14）C]-放射成铃的PEG化聚氰基丙烯酸烷基酯纳米粒子的脑部和脊髓浓度与另一种血液长循环载体（poloxamine 908涂层的聚氰基丙烯酸烷基酯纳米粒子）和常规的非长循环聚氰基丙烯酸烷基酯纳米粒子进行了比较。还研究了CNS中荧光纳米粒子的微观定位，以进一步了解粒子穿透BBB的机理。结果表明，与常规的非PEG化纳米颗粒相比，CNS中尤其是白质中PEG化纳米颗粒的浓度大大增加。另外，在BBB通透性增加和/或巨噬细胞浸润的病理情况下，这种增加明显更高。炎症性病变中的被动扩散和巨噬细胞摄取似乎是此类颗粒进入大脑的基础机制。基于它们在血液中的长期循环特性以及允许细胞相互作用的表面特性，与所有其他测试制剂相比，聚乙二醇化的纳米颗粒可以更大程度地渗入CNS。因此，本文提出了聚乙二醇化的聚氰基丙烯酸酯纳米颗粒，作为神经炎性疾病的新型脑传递系统。

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