Silk-Elastinlike Protein Polymer Liquid Chemoembolic for Localized Release of Doxorubicin and Sorafenib
Silk-Elastinlike Protein Polymer Liquid Chemoembolic for Localized Release of Doxorubicin and Sorafenib
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DOI：
10.1021/acs.molpharmaceut.6b00325
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发表时间：
2016-08-01
影响因子：
4.9
通讯作者：
Ghandehari, Hamidreza
中科院分区：
文献类型：
--
作者：
Poursaid, Azadeh;Jensen, Mark Martin;Ghandehari, Hamidreza
癌症的局部治疗是微创手术，其中治疗直接施用于癌组织。经动脉化疗栓塞（TACE）用于治疗中期肝细胞癌（HCC）。TACE使用栓塞材料阻断血流，同时向肿瘤组织联合给予化疗剂。能够载药的液体栓塞剂处于开发的最前沿，因为它们允许肿瘤脉管系统的更深渗透，增加肿瘤对治疗剂的暴露，并通过占据大直径和小直径血管来抵抗血运重建。在这项工作中，两种用于治疗HCC的化疗药物，多柔比星和索拉非尼，被纳入到由丝弹性蛋白样蛋白聚合物（SELP-815 K）组成的原位凝胶化液体栓塞中。药物的基础形式对SELP的粘度、凝胶化动力学和凝胶刚度没有显著影响：所有这些性质对于可注射液体栓塞剂的成功性能都是必不可少的。体外释放研究表明，SELP液体栓塞剂以治疗相关浓度分别递送阿霉素和索拉非尼（单独或组合）至少14天和30天。
Locoregional therapies for cancer are minimally invasive procedures in which the treatment is administered directly into cancerous tissue. Transarterial chemoembolization (TACE) is used to treat intermediate stage hepatocellular carcinoma (HCC). TACE uses an embolic material to block blood flow while coadministering a chemotherapeutic to the neoplastic tissue. Liquid embolics capable of drug loading are at the forefront of development as they allow for deeper permeation of tumor vasculature, increase neoplasm exposure to therapeutics, and resist revascularization by occupying both large and small diameter vessels. In this work, two chemotherapeutics used in the treatment of HCC, doxorubicin and sorafenib, were incorporated into the in situ gelling liquid embolic composed of a silk-elastinlike protein polymer (SELP-815 K). The base forms of the drugs had no significant effect on the viscosity, the gelation kinetics, and the gel stiffness of the SELP: all properties essential for the successful performance of an injectable liquid embolic. In vitro release studies indicated that the SELP liquid embolic delivered doxorubicin and sorafenib, either alone or in combination, at therapeutically relevant concentrations for a minimum of 14 and 30 days, respectively.