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

Abstract

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 Shi1,2 1State 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