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基于多肽的温敏水凝胶用于抗癌药物的局部和持续递送。

Thermosensitive hydrogels based on polypeptides for localized and sustained delivery of anticancer drugs.

机构信息

Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China; Graduate University of Chinese Academy of Sciences, Beijing 100039, PR China.

出版信息

Biomaterials. 2013 Dec;34(38):10338-47. doi: 10.1016/j.biomaterials.2013.09.064. Epub 2013 Oct 1.

Abstract

Thermosensitive hydrogels based on poly(γ-ethyl-L-glutamate)-poly(ethylene glycol)-poly(γ-ethyl-L-glutamate) triblock copolymers (PELG-PEG-PELG) were prepared for localized and sustained delivery of anticancer drugs. The polypeptide-based hydrogels showed much lower critical gelation concentration than the traditional polyester-based hydrogels. In vivo biocompatibility studies revealed that the in situ formed gels in the subcutaneous layer last for ≈ 21 days, and H&E staining study suggested acceptable biocompatibility of our materials in vivo. Then the hydrogels were tried as injectable implants to encapsulate antitumor drug, paclitaxel (PTX), to assess the in situ anti-tumoral activity using liver cancer xenograft model. The results demonstrated that the PTX-incorporated hydrogels could efficiently suppress the tumor growth, and did not result in obvious damage to normal organs. Therefore, the polypeptide-based thermosensitive hydrogels designed in the present study have great potential to serve as an effective platform for localized anti-cancer drug delivery.

摘要

基于聚(γ-乙基-L-谷氨酸)-聚(乙二醇)-聚(γ-乙基-L-谷氨酸)三嵌段共聚物(PELG-PEG-PELG)的温敏水凝胶被制备用于局部和持续递送抗癌药物。基于多肽的水凝胶表现出比传统聚酯基水凝胶低得多的临界胶凝浓度。体内生物相容性研究表明,在皮下层原位形成的凝胶持续约 21 天,H&E 染色研究表明我们的材料在体内具有可接受的生物相容性。然后,将水凝胶用作可注射植入物来包封抗肿瘤药物紫杉醇(PTX),以使用肝癌异种移植模型评估原位抗肿瘤活性。结果表明,载紫杉醇的水凝胶能够有效抑制肿瘤生长,并且不会对正常器官造成明显损伤。因此,本研究设计的基于多肽的温敏水凝胶具有作为局部抗癌药物递送有效平台的巨大潜力。

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