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Abstract
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.
Acknowledgements
This work was supported by funds from the Zhejiang Provincial Natural Science Foundation of China (Z2100366 and Y2090386), the Joint Project between Zhejiang Province and the Ministry of Health (WKJ20092024), the Zhejiang Provincial Program for the Cultivation of High-level Innovative Health Talents (HJ), the 151 Talent Project of Zhejiang Province (HJ), Zhejiang Medical Research Program (2012ZZ010) and the Doctoral Fund of the Ministry of Education of China (20100101110124).
Disclosure
The authors declare no conflicts of interest in relation to this paper.