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首页> 外文期刊>European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fuer Pharmazeutische Verfahrenstechnik e.V >Polymersomes conjugated to 83-14 monoclonal antibodies: In vitro targeting of brain capillary endothelial cells
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Polymersomes conjugated to 83-14 monoclonal antibodies: In vitro targeting of brain capillary endothelial cells

机译:与83-14单克隆抗体缀合的聚合物小体:脑毛细血管内皮细胞的体外靶向

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摘要

The blood-brain barrier (BBB) remains an obstacle for many drugs to reach the brain. A strategy to cross the BBB is to modify nanocarrier systems with ligands that bind to endogenous receptors expressed at the BBB to induce receptor-mediated transport. The aim of the present study was to investigate the potential of polymersomes composed of the amphiphilic diblock copolymer poly(dimethylsiloxane)-block-poly(2-methyl-2-oxazoline), PDMS-b-PMOXA, for active targeting of brain capillary endothelial cells. We conjugated PDMS-b-PMOXA polymersomes to the anti-human insulin receptor antibody 83-14 and studied their uptake by brain capillary endothelial cells. Transmission electron micrography and light scattering measurements revealed the self-assembly of the block copolymers into 200 nm vesicles after extrusion. Fluorescence correlation spectroscopy was employed to calculate the number of antibodies coupled to one polymersome. Binding and uptake of the polymersomes conjugated to 83-14 mAb were studied in the human BBB in vitro model hCMEC/D3 expressing the human insulin receptor. Competitive inhibition with an excess of free 83-14 mAb demonstrated the specificity of cellular binding and uptake. Our results suggest that PDMS-b-PMOXA polymersomes conjugated to 83-14 mAb may be suitable nanocarriers for drug delivery to the brain.
机译:血脑屏障(BBB)仍然是许多药物到达大脑的障碍。穿越BBB的策略是用与BBB表达的内源性受体结合的配体修饰纳米载体系统,以诱导受体介导的转运。本研究的目的是研究由两亲性二嵌段共聚物聚(二甲基硅氧烷)-嵌段-聚(2-甲基-2-恶唑啉),PDMS-b-PMOXA组成的聚合物囊泡对脑毛细血管内皮细胞主动靶向的潜力细胞。我们将PDMS-b-PMOXA多聚体与抗人胰岛素受体抗体83-14结合,并研究了它们被脑毛细血管内皮细胞摄取的情况。透射电子显微镜和光散射测量揭示了挤出后嵌段共聚物自组装成200nm囊泡。荧光相关光谱法用于计算偶联至一个多聚体的抗体数量。在表达人胰岛素受体的人BBB体外模型hCMEC / D3中研究了与83-14 mAb偶联的聚合物囊泡的结合和摄取。用过量的游离83-14 mAb进行竞争性抑制证明了细胞结合和摄取的特异性。我们的结果表明,偶联至83-14 mAb的PDMS-b-PMOXA聚合物囊泡可能是将药物输送到大脑的合适纳米载体。

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