Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, Liaoning, People's Republic of China.
School of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang, 110016, Liaoning, People's Republic of China.
Pharm Res. 2019 May 10;36(7):96. doi: 10.1007/s11095-019-2637-0.
Etoposide is one of the principal chemotherapeutic agents used for the treatment of small cell lung cancer (SCLC). There are some disadvantages of currently available etoposide injections (EI) such as low LD, necessary dilution before clinical application, thus, etoposide lipid emulsion (ELE) was developed and expected to have a comparable or better effect on SCLC.
ELE was prepared through high-pressure homogenization method, and a series of evaluations such as encapsulation efficiency (EE%), in vitro release, stability studies, pharmacokinetics study, safety assessment and pharmacodynamic study were systematically performed.
ELE had high EE% and good stability. Pharmacokinetics study revealed ELE had a longer T compared with EI, which is in agreement with in vitro release in which ELE released slower than EI (EI released over 80% within 12 h, while ELE released 50%). Safety tests showed there was no hematology or significant tendency of accumulated toxicity, and LD of ELE was higher than EI. Furthermore, percentage of tumor inhibition (TI%) of ELE was comparable with EI in the same dose.
Unlike EI, ELE could further increase the dose, which endowed etoposide with a greater potential for cytotoxic agent. LE is a promising delivery system for etoposide.
依托泊苷是治疗小细胞肺癌（SCLC）的主要化疗药物之一。目前市售的依托泊苷注射液（EI）存在一些缺点，如低 LD，临床应用前需要稀释，因此开发了依托泊苷脂质体（ELE），并期望其对 SCLC 具有相当或更好的疗效。
采用高压匀相法制备 ELE，并对其包封率（EE%）、体外释放、稳定性研究、药代动力学研究、安全性评价和药效学研究进行了系统评价。
ELE 具有较高的 EE%和良好的稳定性。药代动力学研究表明，ELE 的 T 较 EI 长，这与体外释放一致，ELE 的释放速度较 EI 慢（EI 在 12 小时内释放超过 80%，而 ELE 释放 50%）。安全性试验表明，ELE 无血液学毒性或明显蓄积毒性倾向，LD 高于 EI。此外，ELE 在相同剂量下的肿瘤抑制率（TI%）与 EI 相当。
与 EI 不同，ELE 可以进一步增加剂量，从而使依托泊苷具有更大的细胞毒性潜力。ELE 是依托泊苷有前途的递药系统。
