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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
  • 62 Downloads

Abstract

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 LD50, 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 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.

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.

KEY WORDS

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

ABBREVIATIONS

AUC(0-∞)

Area under the plasma concentration-time curve

AUC(0-∞) F

AUC of free etoposide

AUC(0-∞) T

AUC of total etoposide

BLE

The blank lipid emulsion

CL

Total plasma clearance

Cmax

Peak plasma concentration

CMC

Critical micelle concentration

DLS

Dynamic light scattering

EE

Encapsulation efficiency

EI

Etoposide injections

ELE

Etoposide lipid emulsion

EPG

Egg yolk phosphatidylglycerol

HCT

Hematocrit

LCT

Long-chain triglyceride

LD50

Median lethal dose

LE

Lipid emulsion

MCH

Mean corpuscular hemoglobin

MCT

Medium-chain triglyceride

MCV

Mean corpuscular volume

NCA

Non-compartmental analysis

NCCN

The National Comprehensive Cancer Network

NC

Negative control

NEUT#

Neutrophil count

PC

Positive control

P.I.

Polydispersity index

PLT

Platelet count

PSD

Particle size distribution

RET#

Reticulocyte count

SCLC

Small cell lung cancer

T1/2

Elimination of half–life

TI%

Percentage of tumor inhibition

WBC

White blood cell count

WB

Wight of body

WT

Weight of tumor

Notes

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

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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