Poursaid Azadeh, Price Robert, Tiede Andrea, Olson Erik, Huo Eugene, McGill Lawrence, Ghandehari Hamidreza, Cappello Joseph
Department of Bioengineering, University of Utah, 36 S. Wasatch Dr., Salt Lake City, UT 84112, USA; Utah Center for Nanomedicine, Nano Institute of Utah, University of Utah, Salt Lake City, UT 84112, USA.
Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USA; Utah Center for Nanomedicine, Nano Institute of Utah, University of Utah, Salt Lake City, UT 84112, USA.
Biomaterials. 2015 Jul;57:142-52. doi: 10.1016/j.biomaterials.2015.04.015. Epub 2015 Apr 28.
Hepatocellular carcinoma annually affects over 700,000 people worldwide and trends indicate increasing prevalence. Patients ineligible for surgery undergo loco-regional treatments such as transarterial chemoembolization (TACE) to selectively target tumoral blood supply. Using a microcatheter, chemotherapeutics are infused followed by an embolic agent, or the drug is encapsulated by the embolic moiety; simultaneously inducing stasis while delivering localized chemotherapy. Presently, several products are used, but no universally accepted system is promoted because very disparate limitations exist. The goal of this investigation was to design and develop in situ gelling recombinant silk-elastinlike protein polymers (SELPs) for TACE. Two SELP compositions, SELP-47K and SELP-815K, with varying lengths of silk and elastin blocks, were investigated to formulate a new embolic that was injectable through commercially available microcatheters. The goal was to develop a composition providing maximal permeation of tumor vasculature while exhibiting effective embolic activity. The SELPs evaluated remain soluble until reaching 37 °C, when irreversible transition ensues forming a solid hydrogel network. SELP-815K formulated at 12% w/w with shear processing demonstrated acceptable rheological properties and clear embolic capability under flow conditions in vitro. A rabbit model showed feasibility of embolization in vivo allowing selective occlusion of lobar hepatic arterial branches.
肝细胞癌每年在全球影响超过70万人，且有趋势表明其患病率在上升。不符合手术条件的患者接受诸如经动脉化疗栓塞术（TACE）等局部区域治疗，以选择性地靶向肿瘤血液供应。使用微导管，先注入化疗药物，随后注入栓塞剂，或者药物被栓塞部分包裹；在进行局部化疗的同时诱导血流淤滞。目前，有几种产品被使用，但由于存在非常不同的局限性，没有推广通用的系统。本研究的目的是设计和开发用于TACE的原位凝胶化重组丝素-弹性蛋白样蛋白聚合物（SELP）。研究了两种具有不同丝素和弹性蛋白嵌段长度的SELP组合物，即SELP-47K和SELP-815K，以配制一种可通过市售微导管注射的新型栓塞剂。目标是开发一种组合物，既能实现肿瘤血管的最大渗透，又能展现有效的栓塞活性。所评估的SELP在达到37°C之前保持可溶，此时会发生不可逆转变，形成固体水凝胶网络。经剪切处理以12% w/w配制的SELP-815K在体外流动条件下表现出可接受的流变学性质和明确的栓塞能力。兔模型显示了体内栓塞的可行性，可实现肝叶动脉分支的选择性闭塞。
