Optimization of mannosylated curcumin-loaded liposomal formulation using Box-Behnken design

Rheumatoid Arthritis (RA) is the most prevalent auto-immune disease that requires targeted therapeutic interventions. Curcumin, despite its potent anti-inflammatory properties, suffers from inadequate bioavailability, limited water solubility, rapid metabolic clearance, which significantly limit its clinical application. This investigation focused on developing and systematically optimizing mannosylated curcumin-loaded liposomes (MA-CurLps) through Box-Behnken design (BBD) methodology. Thin-film hydration method was used to make liposomes and EDC/NHS coupling chemistry was used to surface-modify liposomes with mannose moieties. BBD has investigated three independent variables drug-to-lipid ratio (A), lipid concentration (B), and sonication time (C) and particle size (Y1), zeta potential (Y2), and entrapment efficiency (Y3) as key quality measures. The experiments were carried out in triplicate (n = 3). The quadratic model demonstrated statistical significance for all responses (R² = 0.277–0.520) with non-significant lack-of-fit, and the optimised formulation yielded particle size of 113.73 ± 1.8 nm, zeta potential of −25.7 ± 14 mV, and entrapment efficiency of 89.31 ± 0.9%, with prediction errors below 5% confirming model validity. Multimodal characterisation by FTIR, DSC, XRD, ¹H NMR, and TEM confirmed covalent mannose conjugation and curcumin encapsulation. Sustained drug release over 24 h followed Higuchi kinetics (R² = 0.983), and cell viability above 85% at therapeutic concentrations confirmed the biocompatibility of the formulation. This study presents a well-optimised, physiochemically characterised liposomal formulation for targeted curcumin delivery in RA, with in vivo validation identified as the essential subsequent step.