Self-association of cyclodextrins and cyclodextrin complexes in aqueous solutions

Cyclodextrins (CDs) are oligosaccharides that self-assemble in aqueous solutions to form transient clusters, nanoparticles and small microparticles. The critical aggregation concentration (cac) of the natural alpha CD, beta CD and gamma CD in pure aqueous solutions was estimated to be 25, 8 and 9 mg/ml, respectively. The cac of 2-hydroxypropyl-beta-cyclodextrin (HP beta CD), that consists of mixture of isomers, was estimated to be significantly higher or 118 mg/ml. Addition of chaotropic agents (i.e. that disrupts non-covalent bonds such as hydrogen bonds) to the aqueous media increases the cac. Formation of drug/CD complexes can increase or decrease the cac. Due to the transient nature of the CD clusters and nanoparticles they can be difficult to detect and their presence is frequently ignored. However, they have profound effect on the physiochemical properties of CDs and their pharmaceutical applications. For example, the values of stability constants of drug/CD complexes can be both concentration dependent and method dependent. Like in the case of micelles water-soluble polymers can enhance the solubilizing effect of CDs. Also, formation of drug/CD complex nanoparticles appears to increase the ability of CDs to enhance drug delivery through some mucosal membranes.