Maan Olla, Al-Samydai Ali, Alqaraleh Moath, Nsairat Hamdi, Alsanabrah Alaa, Awwad Oriana, Al-Hiari Yusuf
Pharmacological and Diagnostic Research Centre, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman, Jordan.
Department of Medical Laboratory Sciences, Faculty of Science, Al-Balqa Applied University, Al-Salt, Jordan.
Drug Dev Res. 2025 Sep;86(6):e70155. doi: 10.1002/ddr.70155.
Cancer treatment faces challenges like nonselective toxicity and drug resistance, prompting the need for innovative therapies. This study aimed to develop liposomal formulations for co-delivery of empagliflozin and rutin, evaluating their anticancer and antioxidant efficacy. PEGylated empagliflozin-loaded nanoliposomes (Empa-NLs) and empagliflozin-rutin co-loaded nanoliposomes (Empa-Rut NLs) were synthesized using the thin-film hydration technique. The formulations were characterized for particle size, zeta potential, polydispersity index (PDI), encapsulation efficiency, and stability. Antiproliferative activity was assessed through MTT assay, and inflammatory and oxidative stress markers were evaluated using ELISA. Empa-NLs had a size of 118.9 ± 0.97 nm, zeta potential of -0.135 ± 0.74mV, and PDI of 0.198 ± 0.11, while Empa-Rut NLs measured 133.4 ± 1.01 nm, zeta potential of -8.78 ± 0.85 mV, and PDI of 0.13 ± 0.01, with significant differences (p ≤ 0.01). Encapsulation efficiency was 10.8 ± 0.103% for empagliflozin and 66.92 ± 0.05% for rutin. Both drugs displayed a biphasic release profile. Free empagliflozin showed stronger antiproliferative activity at lower concentrations, while Empa-Rut NLs were more effective at higher concentrations. Empa-NLs upregulated IL-1β and downregulated catalase, while Empa-Rut NLs and rutin reduced IL-1β and increased catalase. VEGF levels were elevated with empagliflozin but decreased in the presence of rutin and Empa-Rut NLs. Co-loading empagliflozin and rutin in nanoliposomes enhanced anticancer efficacy and modulated inflammatory and oxidative stress responses, suggesting that this combined drug delivery system may improve cancer therapy outcomes.
癌症治疗面临着非选择性毒性和耐药性等挑战，这促使人们需要创新疗法。本研究旨在开发用于共递送恩格列净和芦丁的脂质体制剂，评估它们的抗癌和抗氧化功效。采用薄膜水化技术合成了聚乙二醇化载恩格列净纳米脂质体（Empa-NLs）和恩格列净-芦丁共载纳米脂质体（Empa-Rut NLs）。对制剂的粒径、zeta电位、多分散指数（PDI）、包封率和稳定性进行了表征。通过MTT法评估抗增殖活性，并使用ELISA评估炎症和氧化应激标志物。Empa-NLs的粒径为118.9±0.97nm，zeta电位为-0.135±0.74mV，PDI为0.198±0.11，而Empa-Rut NLs的粒径为133.4±1.01nm，zeta电位为-8.78±0.85mV，PDI为0.13±0.01，存在显著差异（p≤0.01）。恩格列净的包封率为10.8±0.103%，芦丁的包封率为66.92±0.05%。两种药物均呈现双相释放曲线。游离恩格列净在较低浓度下显示出较强的抗增殖活性，而Empa-Rut NLs在较高浓度下更有效。Empa-NLs上调IL-1β并下调过氧化氢酶，而Empa-Rut NLs和芦丁降低IL-1β并增加过氧化氢酶。恩格列净使VEGF水平升高，但在芦丁和Empa-Rut NLs存在时降低。将恩格列净和芦丁共载入纳米脂质体可增强抗癌功效并调节炎症和氧化应激反应，表明这种联合药物递送系统可能改善癌症治疗效果。
