Comparative\nAnalysis of Bare and Quercetin-Loaded\nNonionic Block Copolymer Micelles in an Artificial Gastrointestinal\nMedium

Block copolymer micelles have been increasingly used\nfor the solubilization\nand delivery of hydrophobic drugs. There exists a possibility of dissociation\nof micelles and formation of other association structures in contact\nwith the gastrointestinal fluid. In this study, we demonstrated the\neffect of the fed-state intestinal fluid (FeSSIF) upon characteristics\nof bare and quercetin (QCT)-loaded pluronic 123 (P123) micelles. Characterizations\nwere performed using dynamic light scattering (DLS), <sup>1</sup>H\nNMR, heteronuclear single-quantum coherence (HSQC), two-dimensional <sup>1</sup>H–<sup>1</sup>H nuclear Overhauser effect spectroscopy\n(2D-NOESY), and diffusion-ordered spectroscopy (DOSY). In the case\nof bare micelles, we found copolymer–bile salt mixed aggregates\nwithout any noticeable change in size. DOSY data revealed that lecithin\nformed a separate aggregate in the FeSSIF. Complete micellar solubilization\nof QCT could be verified by the disappearance of its proton signals.\nAt higher dose levels, the diffusion coefficient of micelles increased\nin the FeSSIF. We speculate that QCT-induced hydrophobicity and availability\nof FeSSIF components would have driven the formation of small-sized\nmixed assemblies. On the contrary, the diffusion coefficient of micelles\ndecreased with an increase in the QCT load in the medium devoid of\nFeSSIF components. We deduce that lack of lecithin and bile salts\nprecluded the formation of mixed assemblies in this case, and therefore,\nmicelles turned heavier at higher QCT loads. Such insights on self-assembled\nformulations can be valuable in improving their biological performance.