Codelivery of curcumin and doxorubicin by MPEG-PCL results in improved efficacy of systemically administered chemotherapy in mice with lung cancer

Bi-Lan Wang,^1,* Yong-mei Shen,^1,3,* Qiong-wen Zhang,^1,* Yu-li Li,¹ Min Luo,¹ Ze Liu,^1,2 Yan Li,¹ Zhi-yong Qian,¹ Xiang Gao,¹ Hua-shan Shi<sup>1,2

1</sup>State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medicine School, Sichuan University, Chengdu, Sichuan, ²State Key Laboratory of Biotherapy and Department of Head and Neck Oncology, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, ³Sichuang Haoyisheng Pharmacy, Chengdu, People’s Republic of China

^*These authors contributed equally to this work

Abstract: Systemic administration of chemotherapy for cancer often has toxic side effects, limiting the doses that can be used in its treatment. In this study, we developed methoxy poly(ethylene glycol)-poly(caprolactone) (MPEG-PCL) micelles loaded with curcumin and doxorubicin (Cur-Dox/MPEG-PCL) that were tolerated by recipient mice and had enhanced antitumor effects and fewer side effects. It was shown that these Cur-Dox/MPEG-PCL micelles could release curcumin and doxorubicin slowly in vitro. The long circulation time of MPEG-PCL micelles and the slow rate of release of curcumin and doxorubicin in vivo may help to maintain plasma concentrations of active drug. We also demonstrated that Cur-Dox/MPEG-PCL had improved antitumor effects both in vivo and in vitro. The mechanism by which Cur-Dox/MPEG-PCL micelles inhibit lung cancer might involve increased apoptosis of tumor cells and inhibition of tumor angiogenesis. We found advantages using Cur-Dox/MPEG-PCL micelles in the treatment of cancer, with Cur-Dox/MPEG-PCL achieving better inhibition of LL/2 lung cancer growth in vivo and in vitro. Our study indicates that Cur-Dox/MPEG-PCL micelles may be an effective treatment strategy for cancer in the future.

Keywords: methoxy poly(ethylene glycol), poly(caprolactone), curcumin, doxorubicin, micelles, cancer, treatment