Author: Hiral Siteshchandra Desai
Desai, Hiral Siteshchandra, 2021 Development of self-nanomicellizing solid dispersion loaded with combination of Astaxanthin and curcumin to enhance cytotoxic effect against HCT-116 colon cancer cells, Flinders University, College of Medicine and Public Health
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Carotenoid such as Astaxanthin (AST) and phenolic compound such as curcumin (CUR) possess anti-inflammatory, anti-oxidant, anti-cancer, anti-ageing, and anti-coagulant properties. However, both bioactives are poorly soluble in water and hence, all these properties as stated above cannot be exploited for therapeutic purposes at their full potential. In this study self-nanomicellizing, solid dispersion (SD) of AST and CUR was investigated. Since both compounds possess anti-cancer activity, it was hypothesized that a combination of AST and CUR when provided in the form of a self-nanomicellizing solid dispersion it will have a synergistic cytotoxic effect on the colorectal cancer cell line (HCT-116).
This study developed a self-nanomicellizing SD of AST and CUR to investigate its synergistic cytotoxic effect on HCT- 116 colon cancer cells. The solvent evaporation method was used to formulate the SDs for CUR. Whereas, AST was freeze-dried to obtain the SDs after solvent evaporation. Characterization of the SDs using different techniques such as FTIR, SEM, and DSC was carried out. Solubility, entrapment efficiency, and loading ability of the SDs were calculated by HPLC analysis. The cytotoxicity was measured by conducting the MTT assay after 48 h of treatment.
Self-nanomicellizing SD of AST had a solubility of 3.67 μg/ml whereas CUR had a solubility of 5285 μg/ml. The SD of the combination of AST and CUR had CUR within it with the solubility of 128 μg/ml, and AST with 2.85 μg/ml solubility. There was a significant improvement in the solubility of the previously poorly soluble compound. The cytotoxic effect of SD of AST is 85% when dissolved in water and 51.4% when dissolved in DMSO, whereas for SD of CUR it is 85.1% and 92.2% when dissolved in water and DMSO respectively. As hypothesized, SD of the combination of AST and CUR has a synergistic cytotoxic effect of 89.9% and 98.1% when dissolved in water and DMSO and the p-value is 0.0081 (**, p<0.05) when compared against the combination of free AST and CUR. In conclusion, the experimental results showed that the combination of CUR and AST using a self-micellizing drug delivery system can reduce HCT-116 cell’s viability, which could be considered as a promising complementary treatment approach for colon cancer treatment.
Keywords: Self- nanomicellizing, solid dispersion, Astaxanthin, Curcumin, Cytotoxic, HCT- 116, Colon cancer
Subject: Biotechnology thesis
Thesis type: Masters
Completed: 2021
School: College of Medicine and Public Health
Supervisor: Munish Puri