Assembling and de-assembling micelles: competitive interactions of cyclodextrins and drugs with Pluronics

The associative structures of four beta-cyclodextrins (beta CD) derivatives with triblock copolymers of polyethylene oxide (PEO)-polypropylene oxide (PPO)-polyethylene oxide (PEO) (Pluronics) were investigated by small-angle neutron scattering (SANS), wide-angle X-ray scattering (WAXS) and Fourier transform infrared spectroscopy (FTIR). As shown in a previous study (J. Joseph, C. A. Dreiss, T. Cosgrove, and J. S. Pedersen, Langmuir, 2007, 23, 460-466), the addition of increasing amounts of heptakis(2,6-di-O-methyl)-beta CD (hep2,6-beta CD) promoted a progressive break-up of the Pluronic micelles, while three other derivatives studied, namely, heptakis(2,3,6-tri-O-methyl)-beta CD, 2-hydroxyethyl-beta CD and 2-hydroxypropyl-beta CD, did not lead to any visible change. This is attributed to the capacity of beta CD to form pseudopolyrotaxanes with the PPO block and decrease its hydrophobicity, which is highly dependent on the availability of free hydroxyl groups on the beta CD. Since the gradual de-assembly of micelles could be envisaged as a possible trigger to release the drug encapsulated in the micelles, the interaction of two local anaesthetics, lidocaine and benzocaine, with the Pluronics micelles were investigated. Fitting the SANS data with a paracrystalline model showed that the encapsulation of a drug inside the micellar core led to an increase in micellar size as well as the appearance of long-range order in the solutions. Finally, the competitive interactions of beta CD and drug with the polymeric micelles were studied. The presence of a drug inside the micelles reduced the disruptive action of hep2,6-beta CD, which is attributed to both the capacity of the drug to hold the micelles together and to the formation of an inclusion complex between beta CD and the drug.