In Vitro and In Silico Study on the Molecular Encapsulation of α-Tocopherol in a Large-Ring Cyclodextrin

• Published in: International journal of molecular sciences Vol. 24; no. 5; p. 4425
• Main Authors: Sangkhawasi, Mattanun, Kerdpol, Khanittha, Ismail, Abbas, Nutho, Bodee, Hanpiboon, Chonnikan, Wolschann, Peter, Krusong, Kuakarun, Rungrotmongkol, Thanyada, Hannongbua, Supot
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 23-02-2023; MDPI
• Subjects: alpha-Tocopherol; Analysis; Antioxidants; Aqueous solutions; Cage molecules; Complex formation; Computer applications; Cosmetics industry; Cyclodextrin; Cyclodextrins; Dextrins; Dipeptidyl Peptidase 4; Dipeptidyl-peptidase IV; Encapsulation; Food industry; inclusion complex; Inclusion complexes; Investigations; large-ring cyclodextrins (LR-CDs); Molecular dynamics; molecular dynamics simulation; Pharmaceutical industry; phase solubility; Ratios; Simulation; Solubility; Stoichiometry; Systems stability; Tocopherol; Tocopherols; Vitamin E; α-tocopherol; Thailand; inclusion complex; phase solubility; molecular dynamics simulation; large-ring cyclodextrins (LR-CDs); α-tocopherol
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24054425

α-tocopherol is the physiologically most active form of vitamin E, with numerous biological activities, such as significant antioxidant activity, anticancer capabilities, and anti-aging properties. However, its low water solubility has limited its potential use in the food, cosmetic, and pharmaceutical industries. One possible strategy for addressing this issue is the use of a supramolecular complex with large-ring cyclodextrins (LR-CDs). In this study, the phase solubility of the CD26/α-tocopherol complex was investigated to assess the possible ratios between host and guest in the solution phase. Next, the host-guest association of the CD26/α-tocopherol complex at different ratios of 1:2, 1:4, 1:6, 2:1, 4:1, and 6:1 was studied by all-atom molecular dynamics (MD) simulations. At 1:2 ratio, two α-tocopherol units interact spontaneously with CD26, forming an inclusion complex, as supported by the experimental data. In the 2:1 ratio, a single α-tocopherol unit was encapsulated by two CD26 molecules. In comparison, increasing the number of α-tocopherol or CD26 molecules above two led to self-aggregation and consequently limited the solubility of α-tocopherol. The computational and experimental results indicate that a 1:2 ratio could be the most suitable stoichiometry to use in the CD26/α-tocopherol complex to improve α-tocopherol solubility and stability in inclusion complex formation.