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活体神经影像学揭示了经修饰的两亲性聚 N-乙烯基吡咯烷酮纳米颗粒通过血视网膜屏障转运亲脂性货物。

Live Neuroimaging Reveals the Transport of Lipophilic Cargo Through the Blood-Retina Barrier with Modified Amphiphilic Poly-N-Vinylpyrrolidone Nanoparticles.

机构信息

Institute of Medical Psychology, Otto von Guericke University of Magdeburg, Leipzigerstr. 44, 39120, Magdeburg, Germany.

ArivisAG, Am Kabutzenhof 21, 18057, Rostock, Germany.

出版信息

J Biomed Nanotechnol. 2021 May 1;17(5):846-858. doi: 10.1166/jbn.2021.3073.

DOI:10.1166/jbn.2021.3073
PMID:34082871
Abstract

The blood-retina barrier (BRB), analogous to the blood-brain barrier, is a major hurdle for the passage of drugs from the blood to the central nervous system. Here, we designed polymeric nanoparticles from amphiphilic poly-/V-vinylpyrrolidone (Amph-PVP NPs) as a new carrier-system and investigated their ability to pass the BRB using a live neuroimaging system for the retina in rats and wholemounted retinae preparation. Amph-PVP NPs were loaded with hydrophobic fluorescent markers as a surrogate for hydrophobic drugs. Linking these NPs with the hydrophobic fluorescence marker Carboxyfluorescein-succinimidyl-ester (CFSE) to the surface, induced the passage of the cargo into the retina tissue. In particular, we observed a substantial internalization of the CFSE-linked NPs into blood cells. We propose surface- modified Amph-PVP NPs as a potential new nano-carrier platform to target posterior eye and potentially brain diseases while camouflaged by blood cells.

摘要

血视网膜屏障(BRB)类似于血脑屏障,是药物从血液进入中枢神经系统的主要障碍。在这里,我们设计了两亲性聚/ V- 乙烯基吡咯烷酮(Amph-PVP NPs)的聚合物纳米粒作为一种新的载体系统,并使用大鼠视网膜活体神经成像系统和全视网膜铺片制备研究了它们通过 BRB 的能力。Amph-PVP NPs 被加载疏水性荧光标记物作为疏水性药物的替代物。将这些 NP 与疏水性荧光标记物羧基荧光素琥珀酰亚胺酯(CFSE)连接到表面上,诱导货物进入视网膜组织。特别是,我们观察到 CFSE 连接的 NPs 大量内化到血细胞中。我们提出表面修饰的 Amph-PVP NPs 作为一种有前途的新型纳米载体平台,用于靶向眼部后部和潜在的脑部疾病,同时被血细胞伪装。

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