Oleiwi Maryam Abdulmaged, Al-Samydai Ali, Al-Kabariti Aya Y, Al Azzam Khaldun M, Carradori Simone, Alshaer Walhan
Pharmacological and Diagnostic Research Centre, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman 19328, Jordan.
Department of Biopharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman 19328, Jordan.
Adv Pharm Bull. 2025 Jun 28;15(2):371-389. doi: 10.34172/apb.025.43681. eCollection 2025 Jul.
Breast cancer is the leading cause of cancer-related deaths among women. Chemotherapy faces challenges such as systemic toxicity and multidrug resistance. Advances in nanotechnology have led researchers to develop safer and more efficient cancer treatment methods.
The thin-film hydration method was employed to synthesize PEGylated nanoliposomes (NLs) loaded with raloxifene (RLX) and a combination of RLX and rutin. The NLs were characterized using a Zetasizer® instrument, transmission electron microscopy (TEM), and high-performance liquid chromatography (HPLC) analysis. The encapsulation of RLX and rutin was confirmed, and cell viability assays were conducted against breast cancer and normal endothelial cell lines.
The encapsulation efficiency significantly increased in the mixed formulation, with RLX reaching 91.28% and rutin 78.12%, indicating successful encapsulation. These NLs remained stable for up to two months at room temperature and one month at 4°C, demonstrating a biphasic release pattern. After 24 hours, approximately 17% of RLX was released from the NLs and 25% from the mixed NLs. In contrast, 55% of rutin was released from the NLs and 70.4% from the mixed NLs within 72 hours. The inclusion of rutin or RLX in the liposomal formulation reduced cytotoxicity against breast cancer cell lines, as indicated by the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. However, it improved safety in normal human cells and tissues.
PEGylated NLs loaded with RLX and rutin demonstrated safe anti-breast cancer effects, outperforming mixed NLs, suggesting the potential for a safer and more targeted treatment. Further investigations are needed into clinical translation.
乳腺癌是女性癌症相关死亡的主要原因。化疗面临全身毒性和多药耐药等挑战。纳米技术的进步促使研究人员开发更安全、更有效的癌症治疗方法。
采用薄膜水化法合成负载雷洛昔芬（RLX）以及RLX与芦丁组合的聚乙二醇化纳米脂质体（NLs）。使用Zetasizer®仪器、透射电子显微镜（TEM）和高效液相色谱（HPLC）分析对NLs进行表征。确认了RLX和芦丁的包封情况，并针对乳腺癌细胞系和正常内皮细胞系进行了细胞活力测定。
混合制剂中的包封效率显著提高，RLX达到91.28%，芦丁达到78.12%，表明包封成功。这些NLs在室温下可稳定保存长达两个月，并在4°C下稳定保存一个月，呈现双相释放模式。24小时后，约17%的RLX从NLs中释放，25%从混合NLs中释放。相比之下，72小时内55%的芦丁从NLs中释放，70.4%从混合NLs中释放。脂质体制剂中加入芦丁或RLX降低了对乳腺癌细胞系的细胞毒性，3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）试验表明了这一点。然而，它提高了对正常人体细胞和组织的安全性。
负载RLX和芦丁的聚乙二醇化NLs显示出安全的抗乳腺癌作用，优于混合NLs，表明具有更安全、更有针对性治疗的潜力。需要进一步进行临床转化研究。
