Preparation and in vivo safety evaluations of antileukemic homoharringtonine-loaded PEGylated liposomes

Abstract

In order to improve the in vivo safety and specific delivery efficiency of the antileukemic homoharringtonine (HHT) at the targets, the long-circulating PEGylated liposomes loaded with HHT (LCLipo-HHT) were prepared. Their physical characteristics, in vitro drug release, in vivo pharmacokinetic properties and elementary toxicity were evaluated. The mean diameter of the prepared LCLipo-HHT is 75.6 ± 3.2 nm and the zeta potential is −16.9 ± 2.5 mV. The entrapment efficiency of HHT in the liposomes is 69.5 ± 1.7%. In pharmacokinetic experiments, an increased plasma concentration as well as blood circulation time was obtained when distearoyl phosphoethanolamine-PEG 2000 lipid was added in the formulation, which results in enhancing drug delivery efficiency. Hemolysis test, vascular irritation test and acute toxicity test were used to demonstrate toxicity of LCLipo-HHT. Compared with clinical HHT injection dosage, LCLipo-HHT indicated no vascular irritation, good hemocompatibility, as well as much better safety. Therefore, the prepared LCLipo-HHT can be used as a promising anticancer formulation for antileukemic therapy in the future.

Keywords:

• Homoharringtonine
• PEGylated liposome
• long-circulation
• leukemia
• safety

Acknowledgements

This work was supported by the National Important Science Research Program of China [No. 2013CB733804], National Natural Science Foundation of China for Key Project of International Cooperation [61420106012], National Natural Science Foundation of China [31370019, 81301870, 81473160], Natural Science Foundation of Anhui Province [1508085MH203] and Collaborative Innovation Center of Suzhou Nano Science and Technology as well as Collaborative Innovation Center of Dendrobium Industrialization of Anhui Province.

Disclosure statement

The authors have declared that no competing interest exists.

Additional information

Funding

This work was supported by the National Important Science Research Program of China [No. 2013CB733804], National Natural Science Foundation of China for Key Project of International Cooperation [61420106012], National Natural Science Foundation of China [31370019, 81301870, 81473160], Natural Science Foundation of Anhui Province [1508085MH203] and Collaborative Innovation Center of Suzhou Nano Science and Technology as well as Collaborative Innovation Center of Dendrobium Industrialization of Anhui Province.