Development and evaluation of targeted liposomes for improved doxorubicin and quercetin delivery for MDR breast cancer.

IF 3.4 Q2 PHARMACOLOGY & PHARMACY

Therapeutic delivery Pub Date : 2025-10-01 Epub Date: 2025-10-14 DOI:10.1080/20415990.2025.2570635

Shreastha Gautam, Rashmi Maurya, Preeti Patel, Ghanshyam Das Gupta, Balak Das Kurmi

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引用次数: 0

Abstract

Introduction: Breast cancer remains one of the leading causes of cancer-related deaths among women worldwide. Despite the availability of chemotherapeutics, such as doxorubicin, treatment efficacy, is often hampered by multidrug resistance, largely driven by efflux transporters like P-glycoprotein.

Aim & objectives: This study aimed to develop and evaluate a targeted liposomal system for the co-delivery of doxorubicin and quercetin to overcome multidrug resistance in breast cancer cells. The objective was to enhance therapeutic efficacy while minimizing systemic toxicity.

Method: Liposomes were prepared using the thin-film hydration method and optimized via Box-Behnken Design. Two formulations, doxorubicin and quercetin liposomes (DOX-QCT-LIPO) and Trastuzumab conjugated (TmAb-DOX-QCT-LIPO), were characterized for vesicle size, PDI, and entrapment efficiency. Their cytotoxicity (MTT assay) and cellular uptake (FACS) were tested in MCF-7 and MCF-7/ADR cell lines.

Results: Optimized formulations exhibited nanoscale size, uniform distribution, and high drug encapsulation. Tmab-DOX-QCT-LIPO showed significantly enhanced cytotoxicity and uptake in MDR breast cancer cells compared to free DOX and non-targeted liposomes, indicating effective bypass of efflux mechanisms via HER2-mediated endocytosis.

Conclusion: TmAb-DOX-QCT-LIPO demonstrated superior anticancer potential by integrating dual-drug loading, P-gp inhibition, and HER2-targeted uptake, offering a promising therapeutic strategy against MDR breast cancer.

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靶向脂质体用于改善多药耐多药乳腺癌阿霉素和槲皮素递送的开发和评价。

导言：乳腺癌仍然是全世界妇女癌症相关死亡的主要原因之一。尽管有多柔比星等化疗药物，但治疗效果经常受到多药耐药的影响，多药耐药主要是由p -糖蛋白等外排转运蛋白驱动的。目的：本研究旨在开发和评估一种靶向脂质体系统，用于共同递送阿霉素和槲皮素，以克服乳腺癌细胞的多药耐药。目的是提高治疗效果，同时尽量减少全身毒性。方法：采用薄膜水化法制备脂质体，并采用Box-Behnken设计优化。两种制剂，阿霉素和槲皮素脂质体（DOX-QCT-LIPO）和曲妥珠单抗偶联（TmAb-DOX-QCT-LIPO），表征囊泡大小，PDI和包封效率。在MCF-7和MCF-7/ADR细胞株中检测了它们的细胞毒性（MTT法）和细胞摄取（FACS）。结果：优化后的配方具有纳米级尺寸、均匀分布、高包封性等特点。与游离DOX和非靶向脂质体相比，Tmab-DOX-QCT-LIPO在耐多药乳腺癌细胞中的细胞毒性和摄取显著增强，表明通过her2介导的内吞作用有效绕过外排机制。结论：TmAb-DOX-QCT-LIPO通过整合双药负载、P-gp抑制和her2靶向摄取，显示出卓越的抗癌潜力，为治疗耐多药乳腺癌提供了一种有希望的治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Therapeutic delivery PHARMACOLOGY & PHARMACY-

CiteScore

5.50

自引率

0.00%

发文量

期刊介绍： Delivering therapeutics in a way that is right for the patient - safe, painless, reliable, targeted, efficient and cost effective - is the fundamental aim of scientists working in this area. Correspondingly, this evolving field has already yielded a diversity of delivery methods, including injectors, controlled release formulations, drug eluting implants and transdermal patches. Rapid technological advances and the desire to improve the efficacy and safety profile of existing medications by specific targeting to the site of action, combined with the drive to improve patient compliance, continue to fuel rapid research progress. Furthermore, the emergence of cell-based therapeutics and biopharmaceuticals such as proteins, peptides and nucleotides presents scientists with new and exciting challenges for the application of therapeutic delivery science and technology. Successful delivery strategies increasingly rely upon collaboration across a diversity of fields, including biology, chemistry, pharmacology, nanotechnology, physiology, materials science and engineering. Therapeutic Delivery recognizes the importance of this diverse research platform and encourages the publication of articles that reflect the highly interdisciplinary nature of the field. In a highly competitive industry, Therapeutic Delivery provides the busy researcher with a forum for the rapid publication of original research and critical reviews of all the latest relevant and significant developments, and focuses on how the technological, pharmacological, clinical and physiological aspects come together to successfully deliver modern therapeutics to patients. The journal delivers this essential information in concise, at-a-glance article formats that are readily accessible to the full spectrum of therapeutic delivery researchers.