Characterization of Thymoquinone-Sulfobutylether-β-Cyclodextrin Inclusion Complex for Anticancer Applications

Abstract

Thymoquinone (TQ) is a quinone derived from the black seed Nigella sativa and has been extensively studied in pharmaceutical and nutraceutical research due to its therapeutic potential and pharmacological properties. Although the chemopreventive and potential anticancer effects of TQ have been reported, its limited solubility and poor delivery remain the major limitations. In this study, we aimed to characterize the inclusion complexes of TQ with Sulfobutylether-β-cyclodextrin (SBE-β-CD) at four different temperatures (293–318 K). Additionally, we compared the antiproliferative activity of TQ alone to TQ complexed with SBE-β-CD on six different cancer cell lines, including colon, breast, and liver cancer cells (HCT-116, HT-29, MDA-MB-231, MCF-7, SK-BR-3, and HepG2), using an MTT assay. We calculated the thermodynamic parameters (ΔH, ΔS, and ΔG) using the van’t Holf equation. The inclusion complexes were characterized by X-ray diffraction (XRD), Fourier transforms infrared (FT-IR), and molecular dynamics using the PM6 model. Our findings revealed that the solubility of TQ was improved by ≥60 folds, allowing TQ to penetrate completely into the cavity of SBE-β-CD. The IC50 values of TQ/SBE-β-CD ranged from 0.1 ± 0.01 µg/mL against SK-BR-3 human breast cancer cells to 1.2 ± 0.16 µg/mL against HCT-116 human colorectal cancer cells, depending on the cell line. In comparison, the IC50 values of TQ alone ranged from 0.2 ± 0.01 µg/mL to 4.7 ± 0.21 µg/mL. Overall, our results suggest that SBE-β-CD can enhance the anticancer effect of TQ by increasing its solubility and bioavailability and cellular uptake. However, further studies are necessary to fully understand the underlying mechanisms and potential side effects of using SBE-β-CD as a drug delivery system for TQ.

Formulation of Silymarin-β Cyclodextrin-TPGS Inclusion Complex: Physicochemical Characterization, Molecular Docking, and Cell Viability Assessment against Breast Cancer Cell Lines

“…The phase solubility diagram was found to be of three types based on solubility: A L type (increase in CD concentration led to drug enhancement), A P type (CD more effective at high concentrations), and A N type (negatively deviated straight line due to CD is more effective at low concentrations). In this study, the graph was found to be of A L type . For both the binary and ternary systems, the slopes of the phase solubility curves were smaller than unity.…”

“…In this study, the graph was found to be of A L type. 39 For both the binary and ternary systems, the slopes of the phase solubility curves were smaller than unity. It was hypothesized that the drug and CD would form 1:1 M stoichiometric inclusion complexes in solution.…”

Enhancing the Anti-Leukemic Potential of Thymoquinone/Sulfobutylether-β-cyclodextrin (SBE-β-CD) Inclusion Complexes

“…Additionally, SBE-β-CD has been successfully investigated for controlled drug release and antibacterial efficacy using nanofibers and nanoparticles techniques [17]. Previously, we investigated the formation of inclusion complexes between TQ and SBE-β-CD to improve the solubility and delivery of TQ, and the results demonstrated that the inclusion complexes significantly enhanced TQ's solubility and exhibited improved anticancer effects, suggesting the potential of SBE-β-CD as a drug delivery system for TQ, though further research is needed [13]. Anticancer therapy focuses on targeting telomeres and telomerase, as they play crucial roles in cancer development.…”

“…By utilizing a nanoformulation approach such as SBE-β-CD, the effectiveness of TQ can be significantly enhanced. Thus, TQ/SBE-β-CD holds great promise as a potential strategy for cancer treatment [13].…”

“…We applied a lyophilization technique to formulate the inclusion complex of thymoquinone with sulfobutylether-β-cyclodextrin (SBE-β-CD), replicating the process detailed in our prior research [12,13]. We mixed a balanced 1:1 molar combination of TQ and SBEβ-CD, dissolving it in 20 mL of ultrapure water.…”