Quantifying the High-Affinity Partitioning of Curcumin in POPC Membranes: Distinguishing Surface Adsorption from...

Understanding the molecular partitioning of hydrophobic drugs into fluid lipid bilayers is critical for designing effective delivery systems; however, conventional thermodynamics often struggles to resolve interactions within highly fluid membranes. This study utilizes curcumin as an intrinsic fluorescence probe to directly quantify membrane partitioning and accessibility in 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC) liposomes. Using a combination of steady-state and time-resolved fluorescence spectroscopy, we report a significant partition coefficient for curcumin in POPC (K_p = 1.98 × 10⁶), a value corroborated by established models of unsaturated DOPC systems, with an average fluorescence lifetime increasing from 219 ps in buffer to 278 ps in POPC. The phase transition temperature of POPC was also successfully detected for the first time using curcumin as a fluorescence reporter. The study further investigates sterol-induced ordering, finding that the incorporation of cholesterol significantly reduces curcumin partitioning─a phenomenon attributed to increased bilayer packing and reduced free volume within the liquid-disordered phase. Regarding polymer-liposome synergy, surface modification with Pluronic F-127 was found to enhance the apparent partition coefficient (K_p = 3.02 × 10⁶), increase the fluorescence lifetime (374 ps), and stabilize the curcumin microenvironment. By strictly determining the Critical Micelle Concentration (CMC), we distinguish between surface adsorption and micellar sequestration, revealing that F-127 reduces nonradiative decay rates. Further microenvironment mapping, utilizing curcumin as a probe, was performed. Quenching and lifetime analysis demonstrate that curcumin remains deeply embedded within the bilayer across all formulations, despite modifications to the membrane surface or order. These results establish a robust spectroscopic framework for probing drug-membrane interactions in fluid-phase phospholipids and highlight how the interplay between bilayer ordering and surface stabilization dictates the photophysical behavior of small-molecule guests.