Zhu Chunxia, Liu Yang, Ji Xiaojun, Si Yaxuan, Tao Xianhao, Zhang Xiaohua, Yin Lifang
Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China.
Department of Pharmaceutics, Nanjing Chia-Tai Tianqing Pharmaceutical Co., Ltd., Nanjing 210046, China.
Pharmaceutics. 2024 Sep 19;16(9):1220. doi: 10.3390/pharmaceutics16091220.
Acute myeloid leukemia (AML) is the most common type of acute leukemia among adults with the recommend therapy of combination of cytarabine and idarubicin in the induction phase. The uncoordinated pharmacokinetics prevent adequate control of drug ratio following systemic administration. Therefore, the dual-loaded liposomes containing cytarabine and idarubicin for synergistic effects were proposed and investigated. The molar ratio of cytarabine and idarubicin for synergistic effects was investigated. The dual-loaded liposomes were prepared and characterized by particle size, zeta potential, encapsulation efficiency, cryo-Transmission electron microscopy (cryo-TEM), and in vitro stability. The in vitro cytotoxicity and cell uptake of liposomes were determined within CCRF-CEM cells. The PK experiments was carried out in male SD rats. The in vivo antitumor effect was carried out within CD-1 nude female mice. The antitumor mechanism of liposomes was investigated. The synergistic molar ratios were found to be in the range of 20:1~40:1. The size distribution of the dual-loaded liposomes was approximately 100 nm with PDI ≤ 0.1, a zeta potential of approximately -30 mV, an entrapment efficiency of cytarabine and idarubicin of >95% with spherical structure and uniform distribution, and in vitro stability for 21 d. The drugs in the liposomes can be quickly uptaken by the leukemia cells. The PK experiments showed that the molar ratio of cytarabine to idarubicin in plasma was maintained at 30:1 within 4 h. The efficacy of liposomes was significantly enhanced. Conclusions: The dual-loaded liposomes containing cytarabine and idarubicin showed enhanced antitumor efficacy.
急性髓系白血病（AML）是成人中最常见的急性白血病类型，诱导期推荐使用阿糖胞苷和伊达比星联合治疗。全身给药后，药物动力学不协调阻碍了药物比例的充分控制。因此，提出并研究了载有阿糖胞苷和伊达比星以产生协同作用的双载脂质体。研究了阿糖胞苷和伊达比星产生协同作用的摩尔比。制备了双载脂质体，并通过粒径、ζ电位、包封率、冷冻透射电子显微镜（cryo-TEM）和体外稳定性进行表征。在CCRF-CEM细胞内测定了脂质体的体外细胞毒性和细胞摄取。在雄性SD大鼠中进行了药代动力学实验。在CD-1雌性裸鼠体内进行了抗肿瘤作用实验。研究了脂质体的抗肿瘤机制。发现协同摩尔比在20:1至40:1范围内。双载脂质体的粒径分布约为100 nm，PDI≤0.1，ζ电位约为-30 mV，阿糖胞苷和伊达比星的包封率>95%，具有球形结构且分布均匀，体外稳定性为21天。脂质体中的药物可被白血病细胞快速摄取。药代动力学实验表明，血浆中阿糖胞苷与伊达比星的摩尔比在4小时内维持在30:1。脂质体的疗效显著增强。结论：载有阿糖胞苷和伊达比星的双载脂质体显示出增强的抗肿瘤疗效。
