Thermosensitive injectable hydrogel enhances the antitumor effect of embelin in mouse hepatocellular carcinoma.

Abstract

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/PECT(gel) based on the amphiphilic triblock copolymer of poly (ε-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone)-poly (ethylene glycol)-poly (ε-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone) (PECT). The cytotoxicity and the antitumor effects of Embelin/PECT(gel) 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/PECT(gel) , showing a higher cytotoxicity for H22 cells in vitro compared with free embelin. The aqueous solution of Embelin/PECT(gel) 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/PECT(gel) 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/PECT(gel) , as a drug delivery system in liver, represents a novel therapeutic drug candidate for the clinical treatment of advanced hepatocellular carcinoma.

• Authors: Meiyu Peng, Shuxin Xu, Yong Zhang, Lijuan Zhang, Bingqing Huang, Shuyu Fu, Zhenyi Xue, Yurong Da, Yun Dai, Liang Qiao, Anjie Dong, Rongxin Zhang, Wenbo Meng
• Journal: Journal of pharmaceutical sciences (J Pharm Sci) Vol. 103 Issue 3 Pg. 965-73 (Mar 2014) ISSN: 1520-6017 [Electronic] United States
• PMID: 24481745 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Chemical References

• Antineoplastic Agents, Phytogenic
• Benzoquinones
• Drug Implants
• Hydrogels
• Polyesters
• 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)
• Polyethylene Glycols
• embelin

Topics

• Animals
• Antineoplastic Agents, Phytogenic (administration & dosage, chemistry, pharmacology, therapeutic use)
• Apoptosis (drug effects)
• Benzoquinones (administration & dosage, chemistry, pharmacology, therapeutic use)
• Body Temperature
• Carcinoma, Hepatocellular (drug therapy, pathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Drug Implants
• Hydrogels
• Liver (drug effects, pathology)
• Liver Neoplasms (drug therapy, pathology)
• Male
• Mice
• Mice, Inbred BALB C
• Neoplasm Transplantation
• Phase Transition
• Polyesters (chemistry, toxicity)
• Polyethylene Glycols (chemistry, toxicity)
• Random Allocation
• Solubility
• Toxicity Tests
• Tumor Burden (drug effects)