Analysis of toxicity and anticancer activity of micelles of sodium alginate-curcumin

Abstract

Background

Curcumin is a natural polyphenol with anti-inflammatory, chemopreventive and anticancer activity. However, its high hydrophobicity and poor bioavailability limit its medical application. The development of nanocarriers for curcumin delivery is an attractive approach to overcome its low bioavailability and fast metabolism in the liver. We synthesized a blood compatible alginate-curcumin conjugate, AA-Cur, which formed colloidally stable micelles of approximately 200 nm and, as previously shown, exerted strong cytotoxicity against mouse cancer cell lines. Here we analyze in vivo toxicity and antitumor activity of AA-Cur in two different mouse tumor models.

Method

Potential toxicity of intravenously injected AA-Cur was evaluated by: i) analyses of blood parameters (morphology and biochemistry), ii) histology, iii) DNA integrity (comet assay), and iv) cytokine profiling (flow cytometry). Antitumor activity of AA-Cur was evaluated by measuring the growth of subcutaneously inoculated colon MC38-CEA- or orthotopically injected breast 4T1 tumor cells in control mice vs mice treated with AA-Cur.

Results

Injections of four doses of AA-Cur did not reveal any toxicity of the conjugate, thus indicating the safety of its use. AA-Cur elicited moderate anti-tumor activity toward colon MC38-CEA or breast 4T1 carcinomas.

Conclusion

The tested conjugate of alginate and curcumin, AA-Cur, is non-toxic and safe, but exhibits limited anticancer activity.

Keywords:

• curcumin
• alginate conjugates
• in vivo toxicity
• antitumor activity

Acknowledgments

This work was supported by the Grant for employees over 35 – “Program 35+” no. 35p/4/2016 to MB and The Grant for Young Researchers no. BMN 9/2018 to AK funded by the Faculty of Biochemistry, Biophysics and Biotechnology of the Jagiellonian University in Kraków. The Faculty of Biochemistry, Biophysics and Biotechnology of the Jagiellonian University in Kraków was partner of the Leading National Research Center (KNOW) supported by the Polish Ministry of Science and Higher Education. Agnieszka Cierniak’s present affiliation is now the Department of Biochemistry, Faculty of Medicine and Health Sciences, Andrzej Frycz Modrzewski Krakow University, Kraków, Poland.

Disclosure

The authors report no conflicts of interest in this work.