In this review, based on 250 references, the general chemical principles of direct cyclodextrin–protein interactions are summarized and highlighted, through relevant examples, how these interactions can modify protein functions in vivo, which, despite their huge potential, have been completely unexploited in therapy so far. Finally, a brief overview is given on disorders such as Niemann–Pick type C disease, atherosclerosis, Alzheimer’s and Parkinson’s disease, in which cyclodextrins already have or could have the potential to be active therapeutic agents due to their cholesterol-complexing or direct protein-targeting properties.
While CDs are considered well-tolerated and safe agents in vivo, still unexplored direct protein effects can not only be therapeutically beneficial, but they can even contribute to side effects as off-target actions, which could hinder their autonomous therapeutic use potentially necessitating the development of selective CD derivatives.
Kovacs, T.; Nagy, P.; Panyi, G.; Szente, L.; Varga, Z.; Zakany, F. Cyclodextrins: Only Pharmaceutical Excipients or Full-Fledged Drug Candidates? Pharmaceutics 2022, 14, 2559. https://doi.org/10.3390/pharmaceutics14122559