{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:08:03Z","timestamp":1785434883569,"version":"3.56.0"},"reference-count":174,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"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"},{"id":[{"id":"https:\/\/ror.org\/031d5vw30","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Cyclodextrins (CDs) have gained increasing attention as versatile platforms for enhancing drug delivery to the central nervous system, particularly in overcoming the restrictive properties of the blood\u2013brain barrier (BBB). Owing to their unique cyclic oligosaccharide structure, CDs are capable of forming inclusion complexes with a wide range of therapeutic agents, thereby improving their solubility, stability, and bioavailability. In addition to their role as excipients, growing evidence indicates that CDs can actively modulate biological processes, including membrane fluidity and cholesterol homeostasis, which are critical factors in neurological disorders. This review explores the application of CDs in facilitating drug transport across the BBB through multiple mechanisms, including carrier-mediated transport, receptor-mediated transcytosis, and nanoparticle-based delivery systems. Special emphasis is placed on their use in the treatment of neurodegenerative and neurological diseases, such as Alzheimer\u2019s disease, Parkinson\u2019s disease, multiple sclerosis, Niemann\u2013Pick type C disease, and other central nervous system disorders. In these contexts, CD-based formulations have demonstrated the ability to enhance brain targeting, reduce pathological protein aggregation, and improve therapeutic outcomes in preclinical models. This review uniquely integrates cyclodextrin\u2019s physicochemical properties with specific blood\u2013brain barrier transport mechanisms, proposing a structure\u2013transport\u2013therapy framework that enables a more predictive understanding of brain-targeted drug delivery.<\/jats:p>","DOI":"10.3390\/pharmaceutics18040451","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T14:00:31Z","timestamp":1775570431000},"page":"451","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cyclodextrin-Based Strategies for Brain Drug Delivery: Mechanistic Insights into Blood\u2013Brain Barrier Transport and Therapeutic Applications"],"prefix":"10.3390","volume":"18","author":[{"given":"Pirscoveanu Denisa Floriana","family":"Vasilica","sequence":"first","affiliation":[{"name":"Department of Neurology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pluta Ion","family":"Dorin","sequence":"additional","affiliation":[{"name":"Faculty of Medical and Behavioral Sciences, Constantin Br\u00e2ncu\u0219i University of T\u00e2rgu Jiu, 210185 T\u00e2rgu Jiu, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Vladulescu","sequence":"additional","affiliation":[{"name":"Department of Biology and Environmental Engineering, Faculty of Horticulture, 200585 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Popescu","sequence":"additional","affiliation":[{"name":"Department of Anatomy, ENT Doctor Department of Anatomy, University of Medicine and Pharmacy, 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":"Kristina","family":"Radivojevic","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":"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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7801-5646","authenticated-orcid":false,"given":"\u0218tef\u0103ni\u021ba Bianca","family":"Vintilescu","sequence":"additional","affiliation":[{"name":"Department of Mother and Baby, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4095-6846","authenticated-orcid":false,"given":"Mioara Desdemona","family":"Stepan","sequence":"additional","affiliation":[{"name":"Department of Mother and Baby, 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"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Crini, G., Fourmentin, S., and Lichtfouse, E. 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