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Novel micelle formulation of curcumin for enhancing antitumor activity and inhibiting colorectal cancer stem cells

Authors Wang K, Zhang T, Liu L, Wang XL, Wu P, Chen ZG, Ni C, Zhang JS, Hu FQ, Huang J

Received 6 June 2012

Accepted for publication 27 June 2012

Published 13 August 2012 Volume 2012:7 Pages 4487—4497

DOI https://doi.org/10.2147/IJN.S34702

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Ke Wang,1 Tao Zhang,1 Lina Liu,2 Xiaolei Wang,1 Ping Wu,1 Zhigang Chen,1 Chao Ni,1 Junshu Zhang,1 Fuqiang Hu,4 Jian Huang1,3

1
Cancer Institute, 2Department of Pharmacy, Second Affiliated Hospital (Binjiang Branch), 3Department of Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, 4College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China

Background and methods: Curcumin has extraordinary anticancer properties but has limited use due to its insolubility in water and instability, which leads to low systemic bioavailability. We have developed a novel nanoparticulate formulation of curcumin encapsulated in stearic acid-g-chitosan oligosaccharide (CSO-SA) polymeric micelles to overcome these hurdles.
Results: The synthesized CSO-SA copolymer was able to self-assemble to form nanoscale micelles in aqueous medium. The mean diameter of the curcumin-loaded CSO-SA micelles was 114.7 nm and their mean surface potential was 18.5 mV. Curcumin-loaded CSO-SA micelles showed excellent internalization ability that increased curcumin accumulation in cancer cells. Curcumin-loaded CSO-SA micelles also had potent antiproliferative effects on primary colorectal cancer cells in vitro, resulting in about 6-fold greater inhibition compared with cells treated with a solution containing an equivalent concentration of free curcumin. Intravenous administration of curcumin-loaded CSO-SA micelles marginally suppressed tumor growth but did not increase cytotoxicity to mice, as confirmed by no change in body weight. Most importantly, curcumin-loaded CSO-SA micelles were effective for inhibiting subpopulations of CD44+/CD24+ cells (putative colorectal cancer stem cell markers) both in vitro and in vivo.
Conclusion: The present study identifies an effective and safe means of using curcumin-loaded CSO-SA micelles for cancer therapy.

Keywords: chitosan oligosaccharide, polymeric micelle, curcumin, drug delivery, colorectal cancer, cancer stem cells

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