Preparation of Chitosan Particles as a Delivery System for Tetrahydrocurcumin: β-cyclodextrin Inclusive Compound for Colorectal Carcinoma

Background: Tetrahydrocurcumin is a hydrogenated active metabolite of curcumin that exhibits similar pharmacological effects to curcumin. However, its hydrophobic nature has limited its aqueous solubility and bioavailability. By incorporating the tetrahydrocurcumin into β-cyclodextrin, its physiochemical property can be improved. Objective: To develop a chitosan composite loaded with tetrahydrocurcumin inclusive complex, characterize the developed composites, and evaluate its effectiveness on cancer cells. Methods: Tetrahydrocurcumin was formulated into an inclusive complex with β-cyclodextrin in the ratio of 1:2 (Tetrahydrocurcumin: β-cyclodextrin). The tetrahydrocurcumin inclusive complex loaded chitosan particles (THC IC-loaded CPs) were prepared using ionic gelation and later characterized using FTIR. Cytotoxicity of THC IC-loaded CPs in human colon cancer cells, Caco-2 cells, was examined using RTCA xCELLigence technology. The uptake of these particles by Caco-2 cells was also evaluated via fluorescing microscopy. Results: FTIR results confirmed the formation of the tetrahydrocurcumin inclusive complex and the loading of this complex into chitosan composites. The cytotoxic effect of THC IC-loaded CPs showed a dose-dependent relationship, and the IC50 found was 1.117mM and 0.959mM after 48 and 72 hours, respectively. THC IC-loaded CPs showed an immediate uptake by CaCo-2 cells, and the maximum uptake was observed after 1 hour of incubation. Conclusion: This study showed that THC IC-loaded CPs is a potential drug carrier to deliver tetrahydrocurcumin into cancer cells and able to produce a cytotoxic effect on cancer cells.