Abstract
Silymarin (SLM) is a bioactive, water-insoluble flavonoid reported against different types of cancer. In the present research, the SLM inclusion complex was prepared by the freeze-drying method using different cyclodextrins. The phase solubility study was performed to assess the stability constant and complexation efficiency. The prepared SLM inclusion complexes (F1, F2, and F3) were characterized for different physicochemical and in vitro parameters. Based on the results, the selected inclusion complex (F2) was converted to a topical gel. Finally, it was evaluated for antioxidant, protein denaturation, and cell viability assay (B16F10; skin cancer cell line). The in vitro results were further confirmed by performing a molecular docking study. The phase solubilization results showed the formation of a stable complex with a stability constant value of 548 mol L(-1) (βCD-PLX), 911 mol L(-1) (HP βCD-PLX), and 736 mol L(-1) (M βCD-PLX). A marked increase in release pattern was found from the prepared inclusion complex (80.9 ± 2.2-97.8 ± 3.1%) compared to free SLM (24.1 ± 2.8%). DSC as well as the IR studies confirm the formation of a stable complex. SEM and X-ray diffraction results confirmed the conversion to the amorphous form. The molecular docking studies exhibited the high docking score of SLM with both colchicine-binding sites of the tubulin protein (-6.28 kcal/mol) and complexing agents, viz., βCD (-4.61 kcal/mol), HP βCD (-5.77 kcal/mol), and M βCD (-5.61 kcal/mol). The antioxidant assay results showed that the activity was significantly improved (1.2-1.6 fold) compared to free SLM. The in vitro cell viability assay outcome displayed concentration-dependent activity with a significantly lower IC50 value from F2G2 (145.3 ± 4.2 μg/mL) than free SLM (304.7 ± 5.7 μg/mL). The above conclusions demonstrated that the developed SLM inclusion complex-based gel system could be an ideal delivery system for skin cancer.