期刊
JOURNAL OF PHARMACEUTICAL SCIENCES
卷 103, 期 3, 页码 965-973出版社
WILEY-BLACKWELL
DOI: 10.1002/jps.23885
关键词
embelin; cancer; controlled release; delivery; hydrogels; injectable; thermal gels
资金
- Ministry of Science and Technology of China [2012CB932503, 2011CB933100]
- National Natural Science Foundation of China [91029705, 81172864, 81272317, 81072019, 81371667]
Embelin, an active ingredient of traditional herbal medicine, is used to treat many diseases such as cancer. However, embelin is hydrophobic and insoluble in water, which makes it unsuitable for in vivo applications. In this study, we constructed an embelin-loaded thermosensitive injectable hydrogel system that we named Embelin/PECTgel based on the amphiphilic triblock copolymer of poly (epsilon-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone)-poly (ethylene glycol)-poly (epsilon-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone) (PECT). The cytotoxicity and the antitumor effects of Embelin/PECTgel on mouse hepatic cancers were investigated in vitro and in vivo. Results indicated that embelin was formulated in PECT hydrogel and could be continuously released from Embelin/PECTgel, showing a higher cytotoxicity for H22 cells in vitro compared with free embelin. The aqueous solution of Embelin/PECTgel transformed into gel at the injection site within seconds, which later eroded and degraded over time in vivo. A single local peritumoral injection of Embelin/PECTgel in liver at a low dosage of 0.5 mg per mouse exhibited a significant antitumor effect, which was comparable to the antitumor effect of the embelin solution treatment at a total dose of 6 mg per mouse in mouse hepatic cancer. Embelin/PECTgel, as a drug delivery system in liver, represents a novel therapeutic drug candidate for the clinical treatment of advanced hepatocellular carcinoma. (c) 2014 Wiley Periodicals, Inc.
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