A Comprehensive Preclinical Evaluation of Intravenous Etoposide Lipid Emulsion

  • Xiaoyu Liu
  • Lifeng Luo
  • Pan Qi
  • Yi Liu
  • Tian Yin
  • Jingxin Gou
  • Haibing He
  • Yu ZhangEmail author
  • Xing Tang
Research Paper



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 LD50, 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 T1/2 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 LD50 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.


comprehensive evaluation etoposide lipid emulsion (ele) intravenous pharmacodynamic study safety test 



Area under the plasma concentration-time curve

AUC(0-∞) F

AUC of free etoposide

AUC(0-∞) T

AUC of total etoposide


The blank lipid emulsion


Total plasma clearance


Peak plasma concentration


Critical micelle concentration


Dynamic light scattering


Encapsulation efficiency


Etoposide injections


Etoposide lipid emulsion


Egg yolk phosphatidylglycerol




Long-chain triglyceride


Median lethal dose


Lipid emulsion


Mean corpuscular hemoglobin


Medium-chain triglyceride


Mean corpuscular volume


Non-compartmental analysis


The National Comprehensive Cancer Network


Negative control


Neutrophil count


Positive control


Polydispersity index


Platelet count


Particle size distribution


Reticulocyte count


Small cell lung cancer


Elimination of half–life


Percentage of tumor inhibition


White blood cell count


Wight of body


Weight of tumor



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Authors and Affiliations

  1. 1.Department of Pharmaceutics, School of PharmacyShenyang Pharmaceutical UniversityShenyangPeople’s Republic of China
  2. 2.School of Functional Food and WineShenyang Pharmaceutical UniversityShenyangPeople’s Republic of China

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