Saccharide-Pluronic ® interactions: insights into the structural organization of P104 assemblies

Saccharides are well-established modulators of supramolecular systems and are widely used in designing responsive molecular probes. Their structural diversity and abundant hydroxyl groups enable numerous noncovalent interactions, giving them high molecular specificity essential for biological recognition and modern biosensing. Beyond recognition, saccharides significantly influence micellization by reorganizing the hydrogen-bonding network of water and strengthening hydrophobic interactions that drive micelle formation. Owing to these versatile properties, they are frequently employed as pharmaceutical excipients, particularly in drug delivery. Pluronic® block copolymers (BCPs), known for their tunable self-assembly and excellent solubilization capacity, serve as effective carriers. This study examines how various saccharides, including glucose, fructose, galactose, mannose, mannitol, sorbitol, maltose, and trehalose, modulate the micellar properties and drug-solubilizing ability of a 5 %w/v aqueous Pluronic® P104 solution, a moderately hydrophobic copolymer with strong micelle-forming behavior. To clarify these interactions, micellar characteristics were probed using cloud point (CP) measurements, dynamic light scattering (DLS), small-angle neutron scattering (SANS), proton nuclear magnetic resonance (1H-NMR), and UV-visible spectroscopy. The findings reveal a clear enhancement in micellization and solubilization efficiency in the presence of saccharides. Overall, this work deepens the understanding of saccharide-Pluronic® interactions and supports the development of advanced drug delivery systems using saccharides as functional, synergistic excipients.