Physicochemical Characterization of Liposomal Bilayer Models Loaded with Trans-4-(4′-hydroxy-3′-methoxyphenyl)-5-(1-iodoethyl)dihydrofuran-2-one

Trans-4-(4′-hydroxy-3′-methoxyphenyl)-5-(1-iodoethyl)dihydrofuran-2-one (IL), a vanillin-derived iodolactone with previously demonstrated biological activity, was incorporated into DPPC/cholesterol (DPPC/chol) liposomes to develop and characterize a lipid-based delivery system, with particular emphasis on the relationship between IL incorporation and the biophysical properties of the nanocarrier. The physicochemical stability of formulations containing 2, 5, 10, and 20 mol% IL was assessed using dynamic and electrophoretic light scattering (DLS/ELS), while the loading efficiency (LE%) of the highest IL concentration tested (20 mol%) was determined via ultracentrifugation, liquid–liquid extraction, and subsequent gas chromatography (GC) analysis. The formulation exhibited a high LE% of 87.6 ± 7.8%; however, as potential sedimentation of free IL cannot be ruled out, this value represents an indirect estimate of IL loading and remains a technical limitation of the assay. The effect of IL incorporation on bilayer organization was examined using three fluorescent probes, as well as attenuated total reflectance Fourier-transform infrared spectroscopy. DLS/ELS measurements demonstrated the most favorable colloidal stability for liposomes hydrated with milli-Q water and stored at 4 °C, as reflected by the maintenance of low PDI values, a relatively stable hydrodynamic diameter, and a negative zeta potential throughout the one-month storage period. Fluorescence spectroscopy demonstrated that IL modified the temperature-dependent organization of the DPPC/chol bilayer, with effects particularly evident at the membrane interface and, at elevated temperatures, in the hydrophobic region. Complementary ATR-FTIR analysis indicated that IL interacts with the polar headgroup and glycerol backbone regions without significantly disrupting acyl chain organization. Hemolytic assays further demonstrated the low membrane-damaging activity of IL-loaded liposomes in both crude dispersion fractions and the ultracentrifuged liposomal fraction. These results demonstrate that IL can be efficiently incorporated into DPPC/chol liposomes while maintaining favorable physicochemical stability and low hemolytic potential. The observed effect of the tested compound on bilayer organization without disrupting membrane integrity supports the need for further investigation of lipid formulations containing IL.