Cyclodextrins (CDs) have traditionally been recognized as excipients that enhance solubility and stability of drugs. However, growing evidence shows that CDs themselves can act as active therapeutic agents. Their unique supramolecular properties enable them to interact with biological membranes, mobilize cholesterol, and modulate immune responses. This review highlights four therapeutic areas where CDs demonstrate particular promise. First, in gene and mRNA therapy, cationic CD derivatives form nanoparticles that protect nucleic acids, promote endosomal escape, and achieve targeted delivery. Second, in neurodegenerative disorders such as Niemann–Pick type C and Alzheimer’s disease, hydroxypropyl-β-CD facilitates cholesterol clearance and reduces pathological lipid accumulation. Third, in detoxification, the γ-CD derivative sugammadex exemplifies a clinically approved agent that encapsulates neuromuscular blockers to reverse anesthesia. Finally, CDs have emerged as safe vaccine adjuvants, inducing robust systemic and mucosal immunity with reduced IgE responses compared to alum. Together, these examples illustrate a paradigm shift: CDs are not only versatile excipients but also active molecules with direct therapeutic effects. Future translation will require careful optimization of safety, scalability, and regulatory compliance, but CDs are poised to contribute meaningfully to next-generation medicines.
The therapeutic effecs in cancer treatment, cystic fibrosis, Duchenne Muscular Dystrophy, infectious diseases, neurodegenerative disaeses (Alzheimer’s, Parkinson’s, Huttington’s, Niemann Pick disease) are discussed based on 222 references.
Pirvu AS, Varut RM, Trasca DM, Stoica GA, Radivojevic K, Carmen S, Arsenie CC, Popescu C. Cyclodextrins as Active Therapeutic Agents: Beyond Their Role as Excipients. Pharmaceuticals (Basel). 2025 Oct 21;18(10):1592. https://doi.org/10.3390/ph18101592