The aggregation and structure of D-alpha-tocopheryl polyethylene glycol succinate micelles, TPGS-1000, an amphiphilic derivative of vitamin E, were characterized using scattering and spectroscopic methods, and the impact of different cyclodextrins (CDs) on the self-assembly was investigated, with the view of combining these two versatile pharmaceutical excipients in drug formulations. Combined small-angle neutron scattering (SANS), dynamic light scattering, and time-resolved and steady-state fluorescence emission experiments revealed a core-shell architecture with a high aggregation, number (N-ags approximate to 100) and a highly hydrated poly(ethylene oxide) corona (similar to 11 molecules of solvent per ethylene oxide unit). Micelles form gradually, with no sharp onset. Structural parameters and hydration of the aggregates were surprisingly stable with both temperature and concentration, which is a critical advantage for their use in pharmaceutical: formulations. CDs were shown to affect the self-assembly of TPGS in different ways. Whereas native CDs induced the precipitation of a solid complex (pseudopolyrotaxane), methylated beta-CDs led to different outcomes: constructive (micellar expansion), destructive (micellar rupture), or no effect, depending on the number of substituents and whether the substitution pattern was regular or random on the rims of the macrocycle. Time-resolved SANS studies on mixtures of TPGS with regularly dimethylated beta-CD (DIMEB), which ruptures the micelles, revealed an almost instantaneous demicellization (<100 ms) and showed that the process involved the formation of large aggregates whose size evolved over tithe. Micellar rupture is caused by the formation of a TPGS-DIMEB inclusion complex, involving the incorporation of up to three macrocycles on the tocopherol, as shown by proton nuclear magnetic resonance (NMR) and ROESY NMR. Analysis of NMR. data using Hill's equation revealed that the binding is rather cooperative, with the threading of the CD favoring the subsequent inclusion of additional CDs on the aliphatic moiety.