Shukla Snehal K, Kulkarni Nishant S, Chan Amanda, Parvathaneni Vineela, Farrales Pamela, Muth Aaron, Gupta Vivek
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY 11439, USA.
Department of Biological Sciences, College of Liberal Arts and Sciences, St. John's University, Queens, NY 11439, USA.
Pharmaceutics. 2019 Oct 28;11(11):559. doi: 10.3390/pharmaceutics11110559.
This study aimed at developing metformin hydrochloride (Met) encapsulated liposomal vesicles for enhanced therapeutic outcomes at reduced doses against breast cancer. Liposomal Met was prepared using thin-film hydration through various loading methods; passive loading, active loading, and drug-loaded lipid film. The drug-loaded film method exhibited maximum entrapment efficiency (65%) as compared to active loading (25%) and passive loading (~5%) prepared Met-loaded liposomes. The therapeutic efficacy of these optimized liposomes was evaluated for cellular uptake, cytotoxicity, inhibition of metastatic activity, and apoptosis-inducing activity. Results demonstrated significantly superior activity of positively charged liposomes resulting in reduced IC values, minimal cell migration activity, reduced colony formation, and profound apoptosis-induced activity in breast cancer cells as compared to Met. The anti-tumor activity was investigated using a clinically relevant in vitro tumor simulation model, which confirmed enhanced anti-tumorigenic property of liposomal Met over Met itself. To the authors' knowledge, this is the first report of Met-loaded liposomes for improving the efficacy and therapeutic effect of Met against breast cancer. With the results obtained, it can be speculated that liposomal encapsulation of metformin offers a potentially promising and convenient approach for enhanced efficacy and bioavailability in breast cancer treatment.
本研究旨在开发盐酸二甲双胍（Met）包封的脂质体囊泡，以在降低剂量的情况下增强对乳腺癌的治疗效果。通过各种负载方法，即被动负载、主动负载和载药脂质膜，利用薄膜水化法制备脂质体Met。与主动负载（约25%）和被动负载（约5%）制备的载Met脂质体相比，载药膜法表现出最大的包封效率（约65%）。对这些优化后的脂质体的治疗效果进行了细胞摄取、细胞毒性、转移活性抑制和凋亡诱导活性的评估。结果表明，与Met相比，带正电荷的脂质体具有显著更高的活性，导致IC值降低、细胞迁移活性最小、集落形成减少以及乳腺癌细胞中凋亡诱导活性增强。使用临床相关的体外肿瘤模拟模型研究了抗肿瘤活性，该模型证实脂质体Met比Met本身具有更强的抗肿瘤特性。据作者所知，这是关于载Met脂质体提高Met对乳腺癌疗效和治疗效果的首次报道。根据所获得的结果，可以推测二甲双胍的脂质体包封为提高乳腺癌治疗的疗效和生物利用度提供了一种潜在的、有前景且便捷的方法。
