Poursaid Azadeh, Jensen Mark Martin, Nourbakhsh Ida, Weisenberger Mitchell, Hellgeth John W, Sampath Sujatha, Cappello Joseph, Ghandehari Hamidreza
Department of Bioengineering, University of Utah , Salt Lake City, Utah 84112, United States.
Utah Center for Nanomedicine, Nano Institute of Utah, University of Utah , Salt Lake City, Utah 84112, United States.
Mol Pharm. 2016 Aug 1;13(8):2736-48. doi: 10.1021/acs.molpharmaceut.6b00325. Epub 2016 Jun 29.
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.
癌症的局部区域治疗是将治疗药物直接注入癌组织的微创程序。经动脉化疗栓塞术（TACE）用于治疗中期肝细胞癌（HCC）。TACE在向肿瘤组织联合给药化疗药物的同时，使用栓塞材料阻断血流。能够载药的液体栓塞剂处于研发前沿，因为它们能够更深入地渗透肿瘤血管系统，增加肿瘤对治疗药物的暴露，并通过占据大、小直径血管来抵抗血管再通。在这项研究中，用于治疗HCC的两种化疗药物阿霉素和索拉非尼被纳入由丝弹性蛋白样蛋白聚合物（SELP-815K）组成的原位凝胶化液体栓塞剂中。药物的基础形式对SELP的粘度、凝胶化动力学和凝胶硬度没有显著影响：这些特性对于可注射液体栓塞剂的成功应用至关重要。体外释放研究表明，SELP液体栓塞剂单独或联合递送阿霉素和索拉非尼，在治疗相关浓度下分别至少持续14天和30天。
