Engineering Eucalyptol-in-Water Nanoemulsions with Pluronic F-127: From Formulation to Stability and Function
Lucas Barreteau, Belén Arcos-Álvarez, Angèle Duvieubourg, Hantz Schuffenecker, Alejandro Lucia, Agustina Fañani, Ricardo Ceballos, Natali Fernandez, Ramón G. Rubio, Francisco Ortega, Eduardo GuzmánAbstract
Eucalyptol (1,8-cineole) is a valuable bioactive monoterpene, but its volatility, water immiscibility, and chemical lability limit practical use. Here, we developed eucalyptol-in-water nanoemulsions stabilized by Pluronic F-127 and mapped their composition-dependent phase behavior, structure, and interfacial properties. A pseudoternary formulation map revealed a narrow window of transparent single-phase oil-in-water nanoemulsions, obtained at eucalyptol fractions of 0.01–0.04 (w/w) and Pluronic F-127 fractions up to 0.13 (w/w), whereas higher oil loadings promoted phase separation and excess polymer led to highly viscous or gel-like states. Dynamic light scattering showed nanodroplets with apparent hydrodynamic diameters of about 20–40 nm under optimal conditions, with droplet size increasing as eucalyptol content rose and a second smaller population appearing at higher polymer content, consistent with micellization and structural crowding. Conductivity increased with Pluronic F-127 content, while pH remained near 6.5–6.9 and zeta potential was essentially unchanged, confirming stabilization by a nonionic interfacial layer. Fluorescence spectroscopy indicated two eucalyptol environments, with emission bands centered near 310 and 325 nm, and increasing polymer content reduced fluorescence intensity through self-quenching. Contact angles on polystyrene averaged about 35°, independent of composition, whereas droplets spread almost immediately on glass. In a DPPH assay, nanoemulsions increased radical scavenging relative to free eucalyptol, although excessive Pluronic F-127 reduced this effect by densifying the interfacial shell. Overall, these results define the narrow but well-defined compositional window for carrier-oil-free, kinetically stable O/W eucalyptol nanoemulsions and reveal how oil–polymer interactions govern their formation, stability, and function.