Selective interaction of 2,6-di-O-methyl-β-cyclodextrin and Pluronic F127 micelles leading to micellar rupture: a nuclear magnetic resonance study

Abstract

The triblock-copolymer poly(ethylene oxide)-poly(propyleneoxide)-poly(ethylene oxide) (PEO-PPO-PEO), referred to as Pluronic, is widely studied for its unique aggregation properties and its applications in drug delivery and targeting. In previous studies [Dreiss, C. A.; et al. Soft Matter 2009, 5, 1888-1896], we showed that the interaction of heptakis (2,6-di-O-methyl)-β cyclodextrin (DIMEB) with the triblock-copolymer Pluronic F127 in solutions above the CMC led to complete disruption of the polymeric micelles, while similar β cyclodextrins (βCD) derivatives, heptakis (2,3,6-tri-O-methyl)-βCD (TRIMEB), hydroxypropyl-βCD (HPBCD), and hydroxyethyl-βCD (HEBCD), did not induce micellar break-up. In this work, nuclear magnetic resonance spectroscopy experiments were used to elucidate the nature of the interactions leading to break-up and highlight differences between the four βCD derivatives studied, which could explain the very different outcome observed. Intermolecular nuclear Overhauser enhancements (NOEs) show that both DIMEB and TRIMEB interact selectively with the PPO methyl groups of F127 in a similar way. The interaction is mainly with the external methyl groups in the 6-position of the glucopyranose units of cyclodextrins. However, a weak but detectable interaction with the inner cyclodextrins protons is also observed. These interactions, both with the external surface and with the cavity of βCD, suggest the formation of a loose complex, rather than the widely invoked pseudorotaxane type of inclusion. In addition, these interactions seem to be necessary but not sufficient to induce micellar break-up. Diffusion measurements show decreased diffusivity of DIMEB in the presence of F127 to a larger extent than the other CD derivatives, thus confirming the unique behavior of DIMEB toward F127 polymer. From the diffusion coefficients, an average of 1 DIMEB molecule per 4.2 PO groups of F127 is determined for the highest concentration of DIMEB considered (11 wt % DIMEB dissolved in 5 wt % F127). Micellar break-up is complete at a concentration as low as 1 DIMEB molecule per 8.2 PO units.