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用于治疗急性淋巴细胞白血病的功能化三嵌段共聚物载体

Functionalized Triblock Copolymer Vectors for the Treatment of Acute Lymphoblastic Leukemia.

作者信息

Deller Robert C, Diamanti Paraskevi, Morrison Gabriella, Reilly James, Ede Benjamin C, Richardson Robert, Le Vay Kristian, Collins Andrew M, Blair Allison, Perriman Adam W

机构信息

School of Cellular and Molecular Medicine, University of Bristol , Bristol BS8 1TH, United Kingdom.

Bristol Institute for Transfusion Sciences, NHS Blood and Transplant , Bristol BS34 7QH, United Kingdom.

出版信息

Mol Pharm. 2017 Mar 6;14(3):722-732. doi: 10.1021/acs.molpharmaceut.6b01008. Epub 2017 Feb 16.

Abstract

The chemotherapeutic Parthenolide is an exciting new candidate for the treatment of acute lymphoblastic leukemia, but like many other small-molecule drugs, it has low aqueous solubility. As a consequence, Parthenolide can only be administered clinically in the presence of harmful cosolvents. Accordingly, we describe the synthesis, characterization, and testing of a range of biocompatible triblock copolymer micelles as particle-based delivery vectors for the hydrophobic drug Parthenolide. The drug-loaded particles are produced via an emulsion-to-micelle transition method, and the effects of introducing anionic and cationic surface charges on stability, drug sequestration, biocompatibility, and efficacy are investigated. Significantly, we demonstrate high levels of efficacy in the organic solvent-free systems against human mesenchymal stem cells and primary T-acute lymphoblastic leukemia patient cells, highlighting the effectiveness of the delivery vectors for the treatment of acute lymphoblastic leukemia.

摘要

化疗药物小白菊内酯是治疗急性淋巴细胞白血病的一种令人兴奋的新候选药物,但与许多其他小分子药物一样,它的水溶性较低。因此,小白菊内酯只能在存在有害助溶剂的情况下进行临床给药。据此,我们描述了一系列生物相容性三嵌段共聚物胶束的合成、表征和测试,这些胶束作为疏水性药物小白菊内酯的基于颗粒的递送载体。载药颗粒通过乳液到胶束的转变方法制备,并研究了引入阴离子和阳离子表面电荷对稳定性、药物螯合、生物相容性和疗效的影响。值得注意的是,我们在无有机溶剂的系统中对人间充质干细胞和原发性T急性淋巴细胞白血病患者细胞展示了高水平的疗效,突出了递送载体治疗急性淋巴细胞白血病的有效性。

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