Delivery of eupenifeldin via polymer-coated surgical buttresses prevents local lung cancer recurrence.
Delivery of eupenifeldin via polymer-coated surgical buttresses prevents local lung cancer recurrence.
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DOI：
10.1016/j.jconrel.2021.01.026
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发表时间：
2021-03-10
期刊：
影响因子：
--
通讯作者：
Oberlies NH
中科院分区：
文献类型：
--
作者：
Al Subeh ZY;Chu NQ;Korunes-Miller JT;Tsai LL;Graf TN;Hung YP;Pearce CJ;Grinstaff MW;Colby AH;Colson YL;Oberlies NH
肺癌是全球癌症死亡的主要原因。不幸的是，尽管手术切除和常规化疗，高复发率和低生存率仍然存在。局部给药系统是肺癌治疗的一种有前途的干预措施，具有提高疗效和降低全身毒性的潜力。在这里，我们描述了一种载化疗药物的聚合物支撑物的开发，在肿瘤切除时沿手术切缘沿着植入，用于实现新抗癌剂-优培非定的局部和长期释放。我们制备了五种不同的支撑物制剂，其具有不同量的泽兰非德定和额外的外部空聚合物包衣层（或厚度）以调节药物释放。体外优培菲德定释放曲线取决于外部包衣层的数量，其中最大厚度的制剂表现出接近90天的延长释放。类似地，负载有泽兰素的支撑物制剂对鼠刘易斯肺癌（LLC）和人肺癌（A549）细胞系的长期细胞毒性反映了泽兰素释放曲线，并显示出延长的细胞毒性作用。在切除模型中，装载有泽兰非德定的支撑物显著降低了体内局部肿瘤复发并增加了无病生存期。
Lung cancer is the leading cause of cancer deaths worldwide. Unfortunately, high recurrence rates and poor survival remain despite surgical resection and conventional chemotherapy. Local drug delivery systems are a promising intervention for lung cancer treatment with the potential for improved efficacy with reduced systemic toxicity. Here, we describe the development of a chemotherapy-loaded polymer buttress, to be implanted along the surgical margin at the time of tumor resection, for achieving local and prolonged release of a new anticancer agent, eupenifeldin. We prepared five different formulations of buttresses with varying amounts of eupenifeldin, and additional external empty polymer coating layers (or thicknesses) to modulate drug release. The in vitro eupenifeldin release profile depends on the number of external coating layers with the formulation of the greatest thickness demonstrating a prolonged release approaching 90 days. Similarly, the long-term cytotoxicity of eupenifeldin-loaded buttress formulations against murine Lewis lung carcinoma (LLC) and human lung carcinoma (A549) cell lines mirrors the eupenifeldin release profiles and shows a prolonged cytotoxic effect. Eupenifeldin-loaded buttresses significantly decrease local tumor recurrence in vivo and increase disease-free survival in a resection model.
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