Cyclodextrin nanospheres are a new type of colloidal carrier system that has been intensively studied in the area of pharmacotechnical aspects of drug association. However, the physical stability of this carrier has rarely been investigated, mainly towards the presence of another amphiphilic molecule in ts environment. In this work, the first results relating to the action of solubilizing surfactants on nanospheres prepared from the amphiphilic 2,3-di-O-hexanoyl cyclomaltooctaose [gamma CDC6, average molar degree of substitution (MDS) = 6.25] are described using n-octyl-beta-D-glucopyranoside (OG) as the model. Solubilization experiments were performed by continuous addition of OG into nanosphere suspensions and it was demonstrated that, at a given critical ratio, this non-ionic detergent disrupts the spherical structure of the initial particles. The evidence of the gamma CDC6-OG mixed micelle formation was provided by changes in the turbidity of suspensions with OG addition and by TEM micrographs. Reconstitution of the particles was performed by two detergent removal procedures: water dilution of micellar solutions and detergent dialysis. In both cases, the formation of new aggregates was demonstrated by changes in the turbitity of the initial mixed micelles. TEM micrographs revealed reconstituted nanoparticles. The QELS size and the shape of the particles was dependent on the rate of detergent removal, but not on the initial gamma CDC6 and OG concentrations: fast OG elimination led to the most regular spherical shapes. Finally, the entrapment upon detergent removal of the hydrophobic drug progesterone previously dissolved in the mixed micelles was investigated. In conclusion, all the results demonstrated that detergents can interact with nanospheres in a reversible process. These results will be very useful in stability studies, and also in the pharmacotechnical development of nanospheres constituted. by amphiphilic cyclodextrins. (C) 1998 Elsevier Science B.V.