Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, China.
Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, 110016, China.
AAPS PharmSciTech. 2021 Jan 13;22(1):46. doi: 10.1208/s12249-020-01910-x.
Combination therapy is one of the most common clinical practices in the treatment of malignancies. Synergistic effects, however, are produced only when optimal ratios of combined drugs were delivered to tumor cells. Thus, carriers co-encapsulating of multiple drugs are widely utilized for coordinated delivery. Herein, co-encapsulated pegylated liposomal formulation of mitoxantrone (MIT) and berberine (BER) at an optimal ratio has been developed (MBL) with high encapsulation efficiency (EE) and drug loading in order to achieve the purpose of ratiometric loading and delivery. MBL can not only extend blood circulation but also enhance tumor accumulation for both MIT and BER. More importantly, MBL can maintain the originally desired drug ratio in tumors within 48 h of intravenous injection for synergistic therapy. Compared with the liposomal formulation of MIT-treated group (ML), the progression of tumor growth was inhibited significantly in murine 4T1 breast tumor model after the treatment of MBL, as well as a lower cardiac toxicity. In addition, MBL evidently prolonged the survival of mice with L1210 ascitic tumor model. In summary, such a strategy of co-encapsulated liposomes could improve the clinical applications against multiple cancers.
联合治疗是治疗恶性肿瘤最常见的临床实践之一。然而，只有当联合药物以最佳比例递送到肿瘤细胞时，才会产生协同效应。因此，广泛使用共包封多种药物的载体来进行协同递送。本文开发了米托蒽醌（MIT）和小檗碱（BER）以最佳比例共包封的聚乙二醇化脂质体制剂（MBL），具有高包封效率（EE）和药物载量，以实现比率装载和递送的目的。MBL 不仅可以延长血液循环，还可以增强 MIT 和 BER 在肿瘤中的积累。更重要的是，MBL 可以在静脉注射后 48 小时内维持肿瘤中原本期望的药物比例，从而实现协同治疗。与 MIT 治疗的脂质体制剂（ML）相比，在 4T1 乳腺癌小鼠模型中，MBL 治疗后肿瘤生长的进展明显受到抑制，同时心脏毒性也降低。此外，MBL 明显延长了 L1210 腹水瘤模型中小鼠的存活时间。总之，这种共包封脂质体的策略可以改善针对多种癌症的临床应用。
