Optimization of clove oil-based nanoemulsions for effective curcumin loading: In vitro release and biocompatibility

Curcumin (CUR) has limited aqueous solubility, motivating the development of dispersed formulations for its delivery. Although clove-oil nanoemulsions (CONE) have been reported, the influence of emulsifier choice on the properties of CUR-loaded clove-oil nanoemulsions (CONEs) has received limited direct comparison. This study aimed to prepare CUR-loaded CONEs stabilized with Tween 20 (T20) or whey protein concentrate (WPC 80) and compared their physicochemical characteristics, interactions with bovine serum albumin (BSA), and in vitro release behavior. The optimized CUR-loaded T20 and WPC 80 formulations had hydrodynamic diameters of 16 ± 1 and 225 ± 5 nm, respectively, and CUR entrapment efficiencies of 92.77 ± 1.43% and 95.42 ± 1.72%. Neither formulation showed visible phase separation over 30 days. Spectroscopic measurements indicated interactions between BSA and the CUR-loaded nanoemulsion systems, although the contributions of individual formulation components could not be resolved. Release varied with formulation and pH: after 12 h at pH 5.5, cumulative CUR release was 84.42 ± 0.88% from the T20 formulation and 45.78 ± 0.81% from the WPC 80 formulation. The CUR-loaded WPC 80 NE showed 91.0 ± 0.58% radical-scavenging activity in the ABTS assay and a 15.0 ± 0.28 mm inhibition zone against Klebsiella pneumoniae under the tested conditions. DNA electrophoresis and SDS-PAGE provided preliminary information on interactions with the tested biomolecular models but did not establish overall biocompatibility. These findings show that emulsifier choice influences the measured physicochemical properties and in vitro performance of CUR-loaded CONEs, highlighting the potential of emulsifier-tailored CONEs as delivery systems while supporting the need for further evaluation of their safety and delivery performance.