Formulation, Characterization and In-Vitro Evaluation of Curcumin Loaded Liposome for Colon Drug delivery

Abstract

Curcumin (CUR) exhibits potent anticancer activity but suffers from poor bioavailability and limited colonspecific delivery. The present study reports the development and characterization of unconjugated liposomes (UL) and hyaluronic acid (HA)-conjugated liposomes (HTL) for colon-targeted delivery of CUR. Liposomes were prepared using the thin-film hydration method and conjugated with HA via carbodiimide-mediated coupling. Physicochemical characterization revealed spherical vesicles with mean diameters of 112.1 ± 1.8 nm (UL) and 132.4 ± 3.4 nm (HTL), low polydispersity indices (<0.3), and a shift in zeta potential towards negative values upon HA conjugation. CUR entrapment efficiency was high due to its lipophilicity, though slightly reduced after conjugation. Liposomes were entrapped in calcium alginate beads and coated with Eudragit S-100 to achieve colon-specific release. Beads exhibited pH-dependent swelling and drug release, with negligible release in gastric and intestinal fluids (pH 1.2–4.5) and sustained release in colonic conditions, enhanced by enzymatic degradation of alginate. Ex-vivo studies using HT-29 cells demonstrated significantly higher cellular uptake of HA-conjugated liposomes via CD44 receptor-mediated endocytosis compared to UL. Cytotoxicity assays confirmed enhanced anticancer efficacy of HA-conjugated liposomes, with CUR-loaded conjugated liposomes showing the lowest IC50 values and greatest reduction in cell viability. Overall, HA conjugation improved liposomal stability, colon-specific drug release, and targeted cytotoxicity, underscoring its potential as an effective nanocarrier system for colorectal cancer therapy.