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由聚(乙二醇)-聚丙交酯-聚(乙二醇)三嵌段共聚物制备的纳米管用于联合癌症治疗的生物相容性及紫杉醇/顺铂双负载

Biocompatibility and paclitaxel/cisplatin dual-loading of nanotubes prepared from poly(ethylene glycol)-polylactide-poly(ethylene glycol) triblock copolymers for combination cancer therapy.

作者信息

Shen Xin, Wang Yuandou, Xi Laishun, Su Feng, Li Suming

机构信息

Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao 266061, China.

Institute of High Performance Polymers, Qingdao University of Science and Technology, Qingdao 266042, China.

出版信息

Saudi Pharm J. 2019 Nov;27(7):1025-1035. doi: 10.1016/j.jsps.2019.08.005. Epub 2019 Aug 30.

Abstract

Nanotubes were prepared by self-assembly of the copolymer using co-solvent evaporation method. The biocompatibility of the nanotubes was assessed in comparison with spherical micelles and filomicelles prepared from poly(ethylene glycol)-poly(L-lactide-co-glycolide) (PEG-PLGA) and poly(ethylene glycol)-poly(L-lactide) (PEG-PLA), respectively. Several aspects of biocompatibility of the aggregates were considered, including agar diffusion and MTT assay, release of cytokines, hemolysis, protein adsorption, dynamic clotting , and Zebrafish embryonic compatibility . The nanotubes present good cell compatibility and blood compatibility , and almost no toxicity towards Zebrafish embryos development . Furthermore, dual-loading of hydrophilic cisplatin and hydrophobic paclitaxel was achieved in the nanotubes with high loading content and loading efficiency. The release of both drugs was slower from dual-loaded nanotubes than from single-loaded ones, but the total amount of released drugs in higher for dual-loaded nanotubes than from single-loaded ones. Cellular uptake and inhibition tests showed that the nanotubes were successfully taken up by tumor cells and effectively inhibited cell growth. It is thus concluded that PEG-PLA-PEG nanotubes with outstanding biocompatibility could be promising for co-delivery of hydrophilic and hydrophobic agents in combination cancer therapy.

摘要

通过共溶剂蒸发法自组装共聚物制备纳米管。与分别由聚(乙二醇)-聚(L-丙交酯-共-乙交酯)(PEG-PLGA)和聚(乙二醇)-聚(L-丙交酯)(PEG-PLA)制备的球形胶束和丝状胶束相比,评估了纳米管的生物相容性。考虑了聚集体生物相容性的几个方面,包括琼脂扩散和MTT测定、细胞因子释放、溶血、蛋白质吸附、动态凝血和斑马鱼胚胎相容性。纳米管具有良好的细胞相容性和血液相容性,对斑马鱼胚胎发育几乎没有毒性。此外,在纳米管中实现了亲水性顺铂和疏水性紫杉醇的双重负载,负载含量和负载效率高。双重负载纳米管中两种药物的释放比单一负载纳米管慢,但双重负载纳米管中药物的总释放量比单一负载纳米管高。细胞摄取和抑制试验表明,纳米管被肿瘤细胞成功摄取并有效抑制细胞生长。因此得出结论,具有优异生物相容性的PEG-PLA-PEG纳米管在联合癌症治疗中共同递送亲水性和疏水性药物方面可能具有前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4948/6978636/2280b014b3f6/gr1.jpg

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