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Synergistic co-loading of vincristine improved chemotherapeutic potential of pegylated liposomal doxorubicin against triple negative breast cancer and non-small cell lung cancer
Nanomedicine: Nanotechnology, Biology and Medicine ( IF 4.2 ) Pub Date : 2020-10-16 , DOI: 10.1016/j.nano.2020.102320
Saikat Ghosh 1 , Rohan Lalani 2 , Kuntal Maiti 1 , Shubhadeep Banerjee 3 , Himanshu Bhatt 4 , Yamini Shankar Bobde 4 , Vivek Patel 2 , Swati Biswas 4 , Subhas Bhowmick 1 , Ambikanandan Misra 5
Affiliation  

The current work aims to explore the biological characteristics of vincristine synergistic co-loading into pegylated liposomal doxorubicin in non-indicated modalities of non-small cell lung cancer (NSCLC) and triple negative breast cancer (TNBC). The combinatorial liposome prepared by active co-loading of the drugs against modified ammonium ion gradient exhibited 95% encapsulation of both drugs. The cellular uptake studies using confocal microscopy and flow cytometry showed significantly increased uptake of dual drug formulation as against liposomal doxorubicin. The co-loaded liposome formulation had significantly increased cell cycle arrest in G2/M phase with subsequent apoptosis and reduced cell viability in both tumor cell lines than doxorubicin liposome. This carrier exhibited similar acute toxicity, pharmacokinetic and tissue distribution profiles with significant increase in tumor regression as compared to liposomal doxorubicin. These results indicate that co-encapsulation of vincristine into clinically used pegylated liposomal doxorubicin significantly improved in-vitro and in-vivo therapeutic efficacy against NSCLC and TNBC.



中文翻译:

长春新碱的协同共负载提高了聚乙二醇化脂质体多柔比星对三阴性乳腺癌和非小细胞肺癌的化疗潜力

目前的工作旨在探索长春新碱协同共负载到聚乙二醇化脂质体阿霉素在非小细胞肺癌 (NSCLC) 和三阴性乳腺癌 (TNBC) 的非适应症中的生物学特性。通过对修饰的铵离子梯度主动共负载药物制备的组合脂质体表现出两种药物的 95% 包封率。使用共聚焦显微镜和流式细胞术的细胞摄取研究表明,与脂质体阿霉素相比,双重药物制剂的摄取显着增加。共载脂质体制剂在 G 2 中显着增加细胞周期停滞/M 期与随后的细胞凋亡和比阿霉素脂质体在两种肿瘤细胞系中的细胞活力降低。与脂质体阿霉素相比,该载体表现出相似的急性毒性、药代动力学和组织分布特征,显着增加肿瘤消退。这些结果表明,将长春新碱共包封到临床使用的聚乙二醇化脂质体阿霉素中显着提高对 NSCLC 和 TNBC的体外体内治疗效果。

更新日期:2020-11-04
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