Dieu Le-Ha, Wu Dalin, Palivan Cornelia G, Balasubramanian Vimalkumar, Huwyler Jörg
Department of Pharmaceutical Sciences, Division of Pharmaceutical Technology, University of Basel, Basel, Switzerland.
Department of Chemistry, University of Basel, Basel, Switzerland.
Eur J Pharm Biopharm. 2014 Oct;88(2):316-24. doi: 10.1016/j.ejpb.2014.05.021. Epub 2014 Jun 12.
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.
血脑屏障（BBB）仍然是许多药物进入大脑的障碍。一种跨越血脑屏障的策略是用与血脑屏障上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进行主动靶向的潜力。我们将PDMS-b-PMOXA聚合物囊泡与抗人胰岛素受体抗体83-14偶联，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显示，挤出后嵌段共聚物自组装成200 nm的囊泡。采用荧光相关光谱法计算与一个聚合物囊泡偶联的抗体数量。在表达人胰岛素受体的体外人血脑屏障模型hCMEC/D3中研究了与83-14单克隆抗体偶联的聚合物囊泡的结合和摄取。用过量的游离83-14单克隆抗体进行竞争性抑制，证明了细胞结合和摄取的特异性。我们的结果表明，与83-14单克隆抗体偶联的PDMS-b-PMOXA聚合物囊泡可能是适合向大脑递送药物的纳米载体。
