Drug delivery systems for elemene, its main active ingredient β-elemene, and its derivatives in cancer therapy

Abstract

Bingtao Zhai,1 Yiying Zeng,2–5 Zhaowu Zeng,2–4 Nana Zhang,2–4 Chenxi Li,2–4 Yijun Zeng,2–4 Yu You,1 Shuling Wang,2–4 Xiabin Chen,2–4 Xinbing Sui,2–4 Tian Xie2–4 1College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China; 2Holistic Integrative Pharmacy Institutes, Hangzhou Normal University, Hangzhou, Zhejiang, China; 3Key Laboratory of Elemene Class Anti-cancer Chinese Medicine of Zhejiang Province, Hangzhou, Zhejiang, China; 4Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Hangzhou, Zhejiang, China; 5College of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China Abstract: β-elemene is a noncytotoxic Class II antitumor drug extracted from the traditional Chinese medicine Curcuma wenyujin Y. H. Chen et C. Ling. β-elemene exerts its effects by inhibiting cell proliferation, arresting the cell cycle, inducing cell apoptosis, exerting antiangiogenesis and antimetastasis effects, reversing multiple-drug resistance (MDR), and enhancing the immune system. Elemene injection and oral emulsion have been used to treat various tumors, including cancer of the lung, liver, brain, breast, ovary, gastric, prostate, and other tissues, for >20 years. The safety of both elemene injection and oral emulsion in the clinic has been discussed. Recently, the secondary development of β-elemene has attracted the attention of researchers and made great progress. On the one hand, studies have been carried out on liposome-based systems (including solid lipid nanoparticles [SLNs], nanostructured lipid carriers [NLCs], long-circulating liposomes, active targeting liposomes, and multidrug-loaded liposomes) and emulsion systems (including microemulsions, self-emulsion drug delivery systems [SEDDSs], and active targeting microemulsion) to solve the issues of poor solubility in water, low bioavailability, and severe phlebitis, as well as to improve antitumor efficacy. The pharmacokinetics of different drug delivery systems of β-elemene are also summarized. On the other hand, a number of highly active anticancer β-elemene derivatives have been obtained through modification of the structure of β-elemene. This review focuses on the two drug delivery systems and derivatives of β-elemene for cancer therapy. Keywords: β-elemene, pharmacokinetics, drug delivery system, derivative, safety

Keywords

• β-elemene
• pharmacokinetics
• drug delivery system
• derivative
• safety