Niosomal Co-delivery of Curcumin and Silibinin Enhances Synergistic Anticancer Activity Against Colorectal Cancer Cells

Abstract

Background and purpose: Colorectal cancer (CRC) continues to be a major contributor to cancer-related mortality despite advances in diagnosis and management, highlighting the need for targeted, cost-effective therapies. Phytochemicals like curcumin (Cur) and silibinin (Sil) show promising anticancer effects, supported by preclinical and clinical evidence. Nanocarriers, such as niosomes (Nio), enhance the delivery and bioavailability of these bioactive molecules. The present study evaluates the anticancer potency of Cur and Sil, alone and in combination, in free and niosome-encapsulated forms against HCT116 cells, advancing plant-based nanotherapeutics for CRC. Methods: Niosomes were prepared by thin-film hydration; physicochemical characterization was carried out using DLS, FE-SEM, and FTIR. Cytotoxicity of free, encapsulated, and combined drugs on HCT116 cells was measured using the MTT assay. Cell cycle and apoptosis were analyzed via flow cytometry. Gene expressions of hTERT, BAX, BCL-2, Casp3, Casp7, CCND1, and MMP9 were assessed by qRT-PCR. Cell migration was evaluated with a scratch assay. Results: The synthesized niosomes exhibited suitable physicochemical characteristics for effective drug delivery. MTT assays demonstrated that both curcumin (Cur) and silibinin (Sil) inhibited HCT116 cell proliferation individually. Their combination – whether free, niosome-encapsulated, or niosome-encapsulated with hyaluronic acid – produced a significant decrease in IC₅₀ values. The nano-formulated combination also showed superior induction of apoptosis and cell cycle arrest compared to free drugs. These effects were supported by significant changes in gene expression (p < 0.05). Conclusion: These findings show that co-loaded formulation reduced viability in the tested colorectal cancer cell line, with greater in vitro activity observed for the hyaluronic acid decorated formulation.

Keywords: Silibinin, Colorectal Neoplasms, Nanoparticle, Drug Delivery System, Hyaluronic Acid, Curcumin