Amity Institute of Pharmacy, Amity University Uttar Pradesh, Noida, AUUP 201303, India.
Department of Neuroendocrinology & Experimental Hematology, Chittaranjan National Cancer Institute, Kolkata 700026, India.
Life Sci. 2021 Nov 1;284:119927. doi: 10.1016/j.lfs.2021.119927. Epub 2021 Sep 4.
Among polyphenolic phytoconstituents with anticancer properties, Ellagic acid (EA) is widely reported for its translational potential in vitro but efficient in vivo 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 in vitro and in vivo for breast cancer.
To overcome the challenges of in vivo 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 in vitro against breast cancer cells (MCF7) and in vivo 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 in vitro 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.
在具有抗癌特性的多酚植物化合物中，鞣花酸 (EA) 因其在体外的转化潜力而被广泛报道，但 EA 的有效体内递送一直是一个挑战。我们首次使用吐温 80 包被的纳米递送来评估其在体外和体内对乳腺癌的临床前疗效。
为了克服体内递送的挑战，我们通过离子凝胶化法制备了两批壳聚糖基 EA 纳米制剂（带和不带吐温 80 涂层）。对纳米制剂进行了表征，并进一步在体外评估其对乳腺癌细胞（MCF7）的作用，以及在 EAC 荷瘤小鼠体内评估其抗癌功效，与单独使用鞣花酸进行比较。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尺寸的 EA 包封组成，并表现出良好的药物包封-释放能力。纳米包封的 EA 是生物相容的，并且在体外比单独的 EA 表现出更高的细胞毒性。同样，与单独使用 EA 相比，在纳米-EA 处理的小鼠中观察到更高的肿瘤消退，并且具有吐温 80 涂层的纳米制剂表现出最佳的功效。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 包被的鞣花酸纳米粒子中的协同作用，导致增强了抗乳腺癌肿瘤功效，这可能对其他肿瘤类型也具有转化价值。
