Liposome-chondroitin sulfate/chitosan hybrid system for combinational drug delivery of curcumin and dexamethasone: In vitro anti-cancer activities

This study explored a novel drug delivery system for colorectal cancer (CRC) treatment, focusing on cationic liposomes (L_+ve) and chondroitin sulfate (CHS). The CHS-coated cationic liposome system (CHS@L_+ve) was used to develop different formulations of dexamethasone (DEXA) and curcumin (CURC) using the thin-film hydration technique. The obtained formulations underwent detailed analyses to characterize their physicochemical properties and biological impacts. The formulation designated as CHS-coated DEXA-loaded CURC liposomes CHS_D@L_C, characterized by an average particle size of 80 ± 14 nm, exhibited high encapsulation efficiency (EE%) for both CURC and DEXA. In vitro drug release studies revealed a modified release profile, where DEXA exhibited a higher early release compared to CURC, supporting a staggered immunomodulatory-then-cytotoxic therapeutic strategy. This formulation notably induced 42.18 % S phase arrest and 51.07 % total apoptosis in HCT-116 cells, suggesting effective inhibition of cancer cell proliferation and survival. Mechanistically, this response is effectively linked to the pharmacological action of both agents, as well as extracellular matrix (ECM) modulation and chitosan's mucoadhesive and antibacterial properties. These findings highlight the promise of this dual-drug, polymer-stabilized nanocarrier for targeted CRC treatment, warranting further in vivo validation and clinical translation.