Regulation of the self-assembled nanoscale structures of α-cyclodextrin: encapsulation efficiency and property analysis

α-Cyclodextrin (α-CD) is characterized by its inherent hydrophobic cavity and favorable water solubility, serving as an effective means to enhance the solubility and stability of lipophilic substances. However, the encapsulation efficiency of α-CD inclusion complexes remains relatively low. Therefore,in this study, the regulatory mechanisms of self-assembled nanostructures of α-CD were explored. The structural differences of α-CD self-assembled via hydrogen bonds under various pH conditions were investigated. Taking Vitamin D 3 (VD 3 ) as an example, the impact of these structures on encapsulation efficiency was verified, and the α-CD-VD 3 inclusion complex (IC) was characterized. At pH 9, α-CD exhibited the smallest average particle size (134.36 ± 1.17 nm) and the highest zeta potential (−43.20 ± 1.94 mV), indicating excellent thermal stability. Fourier-transform infrared spectroscopy and proton nuclear magnetic resonance analyses revealed minimal hydrogen bonding between α-CD molecules at this pH, resulting in a maximum encapsulation efficiency of 89.27 % for α-CD-VD 3 . The continuous variation method confirmed the formation of the α-CD-VD 3 IC, with a binding constant of 265.32 M -1 and a Gibbs free energy of −3.30 kcal/mol. The α-CD-VD 3 aqueous solution demonstrated good stability under varying pH and salt ion conditions. In vitro release studies showed that the α-CD-VD 3 IC was stable in simulated gastric fluid and efficiently released VD 3 in simulated intestinal fluid. A stable aqueous delivery system based on the self-assembled structure of α-CD has been successfully developed in this study, which holds broad application prospects in various fields, including pharmaceutical and food sciences.