Thymoquinone-Loaded Lipid Nanocapsules Improve Anticancer Efficacy Following Intraperitoneal Administration in a CT26 Xenograft Model of Colorectal Cancer

Colorectal cancer (CRC) remains a major cause of cancer-related mortality worldwide, with limited treatment options at advanced stages. Thymoquinone (TQ), a natural bioactive compound derived from Nigella sativa , has demonstrated significant anticancer potential but is limited by poor aqueous solubility and low bioavailability. In this study, TQ was successfully encapsulated into lipid nanocapsules (LNCs) to overcome these limitations and enhance its anticancer efficacy after intraperitoneal administration. The LNCs-TQ exhibited a mean diameter of ~60 nm with a high encapsulation efficiency exceeding 85%. Their antiproliferative activity was evaluated in vitro against murine colorectal carcinoma CT26 cells, showing that TQ significantly reduced cell viability compared to free TQ (IC₅₀ : 5 µM vs. 15 µM). In vivo , TQ-LNCs has significantly suppressed tumor growth in a CT26 subcutaneous xenograft mouse model, with a tumor growth inhibition rate of up to 85%. Comet assay and histopathological analysis confirmed enhanced DNA damage and extensive tumor cell necrosis. These results suggest that LNCs-TQ improved the delivery and potency of TQ, making it a promising adjuvant strategy in colorectal cancer therapy.