In vitro and in vivo antitumor effect of gefitinib nanoparticles on human lung cancer

Xiao Ling Ni; Long Xia Chen; Heng Zhang; Bo Yang; Shan Xu; Min Wu; Jing Liu; Ling Lin Yang; Yue Chen; Shao Zhi Fu; Jing Bo Wu

doi:10.1080/10717544.2017.1384862

In vitro and in vivo antitumor effect of gefitinib nanoparticles on human lung cancer

Drug Deliv. 2017 Nov;24(1):1501-1512. doi: 10.1080/10717544.2017.1384862.

Authors

Xiao Ling Ni¹, Long Xia Chen¹, Heng Zhang¹, Bo Yang¹, Shan Xu¹, Min Wu¹, Jing Liu¹, Ling Lin Yang¹, Yue Chen², Shao Zhi Fu¹, Jing Bo Wu¹

Affiliations

¹ a Department of Oncology , the Affiliated hospital of Southwest Medical University , Luzhou , China.
² b Department of Nuclear Medicine , the Affiliated hospital of Southwest Medical University , Luzhou , China.

Abstract

Gefitinib (GEF) is the first epidermal growth factor receptor (EGFR)-targeting agent launched as an anticancer drug. It is an accepted opinion that modifying GEF strong hydrophobicity and poor bioavailability would not only enhance its antitumor effects, but also reduce its side effects. In this study, GEF-loadedpoly(ε-caprolactone)-poly(ethyleneglycol)-poly(ε-caprolactone) (PCEC) -bearing nanoparticles (GEF-NPs) were prepared by a solid dispersion method and characterized. The particle sizes increased with the increase in GEF/PCEC mass ratio in feed. GEF-NPs (10%) were mono-dispersed, smaller than 24 nm, zeta potential was approximately -18 mV, percentage encapsulation and loading, were more than 9% and 92%, respectively, and drug was slowly released but without a biphasic pattern. Microscopy studies of the optimized formulation confirmed that the prepared nanoparticles are spherical in nature. Cytotoxicity results indicated that cell growth inhibition induced by free GEF and GEF-NPs were dose and time dependent. Compared with free GEF, GEF-NPs enhanced antitumor effects, reduced side effects and significantly prolonged survival time in vivo. CD31, ki-67 and EGFR expression were significantly lower in the GEF-NPs group compared with other groups (p< .05). These findings demonstrated that GEF-NPs have the potential to attain superior outcomes and to overcome complications such as organs toxicity, therapeutic resistance and disease relapse.

Keywords: Gefitinib; PCEC; lung cancer; nanoparticles.

MeSH terms

Cell Line, Tumor
Gefitinib
Humans
Lung Neoplasms*
Nanoparticles*
Quinazolines

Substances

Quinazolines
Gefitinib

Grants and funding

This work was supported by the project from Health and Family Planning Commission of Sichuan Province (No. 17PJ557), the research project from Office of Science & Technology and Intellectual Property of Luzhou (No. 2017), the Union Project of Luzhou and Southwest Medical University under Grant (No. 14JC0144 and 2013LZLY-J40).