A Comprehensive Preclinical Evaluation of Intravenous Etoposide Lipid Emulsion

Purpose 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 50 , necessary dilution before clinical application, thus, etoposide lipid emulsion (ELE) was developed and expected to have a comparable or better effect on SCLC. Methods 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. Results ELE had high EE% and good stability. Pharmacokinetics study revealed ELE had a longer T 1/2 F 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 50 of ELE was higher than EI. Furthermore, percentage of tumor inhibition (TI%) of ELE was comparable with EI in the same dose. Conclusions 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.