Self-assembled cyclodextrin aggregates and nanoparticles

Cyclodextrins (CDs) are widely used as enabling pharmaceutical excipients, mainly as solubilizing complexing agents. CDs are cyclic oligosaccharides with hydrophilic outer surface and a somewhat lipophilic central cavity. In aqueous solutions CDs are able to solubilize lipophilic drugs by taking up some lipophilic moiety of the drug molecule into the central cavity, i.e. through formation of hydrophilic inclusion complexes. Recently it has been observed that that other types of CD complexes, such as non-inclusion complexes, are also participating in the CD solubilization of poorly soluble drugs. However, in aqueous solutions CDs are also able self-assemble to form nanosized aggregates that can contribute to their solubilizing properties. At low CD concentrations (at about 1%, w/v) the fraction of CD molecules forming aggregates is insignificant but the aggregation increases rapidly with increasing CD concentration. Also, formation of CD complexes can increase the tendency of CDs to form aggregates and can lead to formation of micellar-type CD aggregates capable to solubilize poorly soluble compounds that do not readily form inclusion complexes. In this article formation of CD aggregates and CD nanoparticles is reviewed with emphasis on the physicochemical properties of self-assembled CDs and CD complexes.