Among polyphenolic phytoconstituents with anticancer properties, Ellagic acid (EA) is widely reported for its translational potential but efficient delivery of EA has been a challenge. We, for the first time, used a tween 80 coated nano delivery of Ellagic acid to evaluate its preclinical efficacy and for breast cancer. To overcome the challenges of delivery, two batches of chitosan-based nanoformulations of EA (with and without tween 80 coating) were prepared by the ionotropic gelation method. The nanoformulations were characterized and further evaluated against breast cancer cells (MCF7) and with EAC tumor-bearing mice for establishing their anticancer efficacy compared to Ellagic acid alone. A quantitative simulation study was undertaken to understand if the observed antitumor efficacy is due to the synergistic efficacy of the Chitosan-Ellagic acid combination. Results revealed that nanoformulations consist of good nano-sized encapsulation of EA and showed good drug entrapment-release capacity. Nano-encapsulated EA is biocompatible and exhibited higher cytotoxicity compared to EA alone. Similarly, significantly higher tumor regression was observed in nano-EA treated mice compared to EA alone, and best efficacy was observed with the nanoformulation with tween 80 coating. Furthermore, nanoformulations showed higher apoptosis in tumor tissues with no significant tissue toxicity in vital organs. We report synergism of Chitosan-Ellagic acid combination in the tween 80 coated nanoparticles of Ellagic acid resulting in enhanced anti-breast tumor efficacy that may be of translational value for other tumor types, too.

中文翻译：

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负载鞣花酸、吐温 80 涂层的壳聚糖纳米粒子作为一种有前景的乳腺癌治疗方法：体外和体内研究


在具有抗癌特性的多酚植物成分中，鞣花酸 (EA) 因其转化潜力而被广泛报道，但 EA 的有效传递一直是一个挑战。我们首次使用吐温 80 涂层纳米鞣花酸来评估其临床前疗效和对乳腺癌的疗效。为了克服交付的挑战，通过离子凝胶法制备了两批基于壳聚糖的 EA 纳米制剂（有和没有吐温 80 涂层）。对纳米制剂进行了表征，并进一步针对乳腺癌细胞 (MCF7) 和 EAC 荷瘤小鼠进行了评估，以确定其与单独的鞣花酸相比的抗癌功效。进行了定量模拟研究，以了解观察到的抗肿瘤功效是否归因于壳聚糖-鞣花酸组合的协同功效。结果表明，纳米制剂由良好的纳米级封装的 EA 组成，并表现出良好的药物包封-释放能力。纳米封装的 EA 具有生物相容性，并且与单独的 EA 相比表现出更高的细胞毒性。同样，与单独使用 EA 相比，在纳米 EA 治疗的小鼠中观察到明显更高的肿瘤消退，并且使用吐温 80 涂层的纳米制剂观察到最佳疗效。此外，纳米制剂在肿瘤组织中显示出更高的细胞凋亡，而在重要器官中没有明显的组织毒性。我们报告了壳聚糖-鞣花酸组合在吐温 80 涂层鞣花酸纳米颗粒中的协同作用，从而增强了抗乳腺肿瘤功效，这对于其他肿瘤类型也可能具有转化价值。