Comparative Analysis of Bare and Quercetin-Loaded Nonionic Block Copolymer Micelles in an Artificial Gastrointestinal Medium

Abstract

Block copolymer micelles have been increasingly used for the solubilization and delivery of hydrophobic drugs. There exists a possibility of dissociation of micelles and formation of other association structures in contact with the gastrointestinal fluid. In this study, we demonstrated the effect of the fed-state intestinal fluid (FeSSIF) upon characteristics of bare and quercetin (QCT)loaded pluronic 123 (P123) micelles. Characterizations were performed using dynamic light scattering (DLS), 1 H NMR, heteronuclear single-quantum coherence (HSQC), two-dimensional 1 H− 1 H nuclear Overhauser effect spectroscopy (2D-NOESY), and diffusion-ordered spectroscopy (DOSY). In the case of bare micelles, we found copolymer−bile salt mixed aggregates without any noticeable change in size. DOSY data revealed that lecithin formed a separate aggregate in the FeSSIF. Complete micellar solubilization of QCT could be verified by the disappearance of its proton signals. At higher dose levels, the diffusion coefficient of micelles increased in the FeSSIF. We speculate that QCT-induced hydrophobicity and availability of FeSSIF components would have driven the formation of small-sized mixed assemblies. On the contrary, the diffusion coefficient of micelles decreased with an increase in the QCT load in the medium devoid of FeSSIF components. We deduce that lack of lecithin and bile salts precluded the formation of mixed assemblies in this case, and therefore, micelles turned heavier at higher QCT loads. Such insights on selfassembled formulations can be valuable in improving their biological performance.