Hydroxypropyl‑β‑cyclodextrin/thymoquinone inclusion complex inhibits non‑small cell lung cancer progression through NF‑κB‑mediated ferroptosis

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Abstract
Thymoquinone (TQ) is a quinone isolated from the black seed Nigella sativa and has been extensively investigated in the pharmaceutical field due to its promising therapeutic value. There have been reports on the potential anti‑cancer properties of TQ, whereas the clinical application of TQ is greatly restricted by its low water solubility and poor delivery. In the present study, TQ was encapsulated into hydroxypropyl‑β‑cyclodextrin (HP‑β‑CD) using the freeze‑drying method to form a TQ/HP‑β‑CD inclusion complex. Then, the TQ/HP‑β‑CD inclusion complex was characterized by Fourier transform infrared, differential scanning calorimetry, X‑ray diffraction and scanning electron microscopy. HP‑β‑CD as an excipient significantly enhances the water solubility of TQ, and TQ/HP‑β‑CD demonstrated excellent biocompatibility on normal cells both in vitro and in vivo. Moreover, the complexation with HP‑β‑CD enhanced the anticancer activity of TQ against non‑small cell lung cancer cells and its mechanism of action is related to ferroptosis mediated by NF‑κB. Such an enhanced cytotoxic effect may be attributed to the effective complexation of TQ in HP‑β‑CD, which enhances its water solubility and bioavailability.

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