{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T20:56:26Z","timestamp":1792443386188,"version":"4.5.0"},"reference-count":222,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T00:00:00Z","timestamp":1761004800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Medicine and Pharmacy of Craiova, Romania"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>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\u2013Pick type C and Alzheimer\u2019s disease, hydroxypropyl-\u03b2-CD facilitates cholesterol clearance and reduces pathological lipid accumulation. Third, in detoxification, the \u03b3-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.<\/jats:p>","DOI":"10.3390\/ph18101592","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T14:53:19Z","timestamp":1761058399000},"page":"1592","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Cyclodextrins as Active Therapeutic Agents: Beyond Their Role as Excipients"],"prefix":"10.3390","volume":"18","author":[{"given":"Andreea Silvia","family":"Pirvu","sequence":"first","affiliation":[{"name":"Department of Biochemistry, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata-Maria","family":"Varut","sequence":"additional","affiliation":[{"name":"Research Methodology Department, Faculty of Pharmacy, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana-Maria","family":"Trasca","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George Alin","family":"Stoica","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Radivojevic","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sirbulet","family":"Carmen","sequence":"additional","affiliation":[{"name":"Department of Anatomy, University of Medicine and Pharmacy, Discipline of Anatomy, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian Cosmin","family":"Arsenie","sequence":"additional","affiliation":[{"name":"Department of Anatomy, University of Medicine and Pharmacy, Discipline of Anatomy, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Popescu","sequence":"additional","affiliation":[{"name":"Department of Anatomy, University of Medicine and Pharmacy, Discipline of Anatomy, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/polysaccharides3010001","article-title":"Cyclodextrins: Structural, Chemical, and Physical Properties, and Applications","volume":"3","author":"Poulson","year":"2022","journal-title":"Polysaccharides"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.jpba.2016.05.009","article-title":"Analytical Characterization of Cyclodextrins: History, Official Methods and Recommended New Techniques","volume":"130","author":"Szente","year":"2016","journal-title":"J. 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