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负载乳铁蛋白的聚乙二醇/聚乳酸嵌段共聚物,用抗转铁蛋白受体抗体靶向治疗阿尔茨海默病

Lactoferrin-Loaded PEG/PLA Block Copolymer Targeted With Anti-Transferrin Receptor Antibodies for Alzheimer Disease.

作者信息

Li Guichen, Sun Xianghong, Wan Xiaona, Wang Dongming

机构信息

Department of Clinical Psychology, Qingdao Mental Health Center, Qingdao, China.

Second Elderly Ward, Qingdao Mental Health Center, Qingdao, China.

出版信息

Dose Response. 2020 Aug 14;18(3):1559325820917836. doi: 10.1177/1559325820917836. eCollection 2020 Jul-Sep.

Abstract

Last few years, struggles have been reported to develop the nanovesicles for drug delivery via the brain-blood barrier (BBB). Novel drugs, for instance, iAβ, are efficient to inhibit the aggregates connected to the treatment of Alzheimer disease and are being evaluated, but most of the reports reflect some drawbacks of the drugs to reach the brain in preferred concentrations owing to the less BBB penetrability of the surface dimensions. In this report, we designed and developed a new approach to enhance the transport of drug via BBB, constructed with lactoferrin (Lf)-coated polyethylene glycol-polylactide nanoparticles (Lf-PPN) with superficial monoclonal antibody-functionalized antitransferrin receptor and anti-Aβ to deliver the iAβ hooked on the brain. The porcine brain capillary endothelial cells were utilized as BBB typically to examine the framework efficacy and toxicity. The cellular uptake of the immuno-nanoparticles with measured conveyance of the iAβ peptide was significantly enhanced and associated with Lf-PPN without monoclonal antibody functionalizations.

摘要

在过去几年中,据报道在开发用于通过血脑屏障(BBB)进行药物递送的纳米囊泡方面存在困难。例如,新型药物iAβ在抑制与阿尔茨海默病治疗相关的聚集体方面很有效,并且正在进行评估,但大多数报告反映出由于药物表面尺寸的血脑屏障穿透性较低,药物难以达到理想浓度到达大脑。在本报告中,我们设计并开发了一种新方法来增强药物通过血脑屏障的转运,该方法构建了乳铁蛋白(Lf)包被的聚乙二醇 - 聚丙交酯纳米颗粒(Lf - PPN),其表面具有单克隆抗体功能化的抗转铁蛋白受体和抗Aβ,以递送附着在大脑上的iAβ。猪脑毛细血管内皮细胞通常被用作血脑屏障来检测该框架的功效和毒性。与未进行单克隆抗体功能化的Lf - PPN相比,免疫纳米颗粒对iAβ肽的细胞摄取量显著增加且与之相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96dd/7430085/1daab0c4946f/10.1177_1559325820917836-fig1.jpg

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