Curcumin–Lipid Interactions in PEGylated vs. Conventional Liposomes: A Combined Fluorescence and EPR Study

Curcumin, a natural polyphenol derived from Curcuma longa, is widely recognized for its therapeutic properties. However, its clinical utility is limited because of poor solubility, rapid degradation and hence low bioavailability. To overcome these issues, nanoformulation approaches, especially PEGylated liposomes, have been explored as advanced delivery systems. PEGylation, which involves attaching polyethylene glycol (PEG) to the liposomal surface, enhances circulation time by creating a steric shield that reduces protein interactions and clearance by the mononuclear phagocyte system (MPS). However, PEG can alter lipid membrane properties, which may in turn affect curcumin’s solubility and distribution within the liposomal bilayer, ultimately reducing its loading efficiency. To ensure that PEG-modified liposomes can be effectively loaded with curcumin, we investigated curcumin–membrane interactions in saturated (DMPC) and unsaturated (POPC) liposomes, both in the presence and absence of PEG. Based on dissociation constants (Kd) obtained from fluorescence spectroscopy measurements, we found that PEGylated DMPC liposomes exhibit the strongest binding affinity for curcumin. Fluorescence quenching experiments showed that curcumin adopts a transbilayer orientation in all membranes examined. Curcumin’s location within PEGylated and non-PEGylated liposomal membranes was further confirmed by examining its effects on membrane properties, including fluidity, polarity, and oxygen transport. These effects were investigated using electron paramagnetic resonance (EPR) spectroscopy with spin labels. The results indicate that PEG does not impose major changes on membrane properties. Curcumin, however, was found to reinforce the liposomal membranes, increase their polarity, and reduce oxygen availability. Overall, the findings suggest that liposomes, particularly those composed of PEGylated DMPC, are effective vehicles for curcumin delivery.