Arsenic trioxide encapsulated liposomes prepared via copper acetate gradient loading method and its antitumor efficiency

• 作者: Chunxiu Liu Cunyang Wang Hui Xu Jia Ma Jianbo Guo Shaoning Wang Yihui Deng
• 来源期刊: 亚洲药物制剂科学(英文)
• 学科: 工学
• 关键词: Arsenic trioxide Liposomes Copper acetate gradient PHARMACOKINETICS Tissue distribution Antitumor activity
• 年，卷（期）: 2020,（3）
• 页码范围: 365-373
• 页数: 9页
• 分类号: TB3

摘要

In this study, arsenic trioxide(ATO) was encapsulated in liposomes via copper acetate(Cu(OAc)2) gradients and high entrapment efficiency of over 80% was obtained. The average particle size and the zeta-potential of the liposomes were detected to be 115.1 ± 29.1 nm and-21.97 ± 0.6 m V, respectively. The TEM images showed rod-like precipitates in the inner aqueous phase, which was supposed be due to the formation of insoluble ATO–Cu complex.The in vitro drug release of ATO–Cu liposomes exhibited a sustained release over 72 h, and the release rates decreased with the increase of the p H of release media. Pharmacokinetic and tissue distribution studies of ATO liposomes showed significantly reduced plasma clearance rate, increased AUC0–12h and T1/2, and improved tumor distribution of As compared to iv administration of ATO solution. The anti-tumor effect of ATO loaded liposomes to S180 tumor-bearing mice was significantly improved with a tumor inhibition rate of 61.2%,meanwhile the toxicity of encapsulated ATO was greatly decreased. In conclusion, ATO can be effectively encapsulated into liposomes by remote loading method via Cu(OAc)2 gradients;the co-administration of ATO and Cu(Ⅱ) via liposomal formulation may find wide applications in the treatment of various tumors.