β-cyclodextrin inclusion complexes with vitamin A and its esters: a comparative experimental and molecular modeling study

Abstract Cyclodextrin (CD) complexation has emerged as a promising approach for enhancing the solubility or/and stability of hydrophobic small molecule substances. In this work the inclusion complexes of Vitamin A (VA), Vitamin A acetate (VAA), and Vitamin A palmitate (VAP) with β-cyclodextrins (β-CDs) were prepared by co-precipitation with freeze-drying methods. Results from FT-IR, NMR, and SEM confirmed the formation of inclusion complexes. Phase solubility diagram study shows β-CD and VA/ VA esters formed clathrate with molecular ratio of 1:1, 1:1, and 2:1, respectively. Among these vitamins tested, free VA has the lowest thermal stability, but it was the highest after embedding with β-CD. β-CD:VA also showed better water solubility. Although VAP achieved the highest increase rate in water solubility among the three vitamins after embedding with β-CD, water solubility of β-CD:VAP was still relatively small due to the poor water solubility of free VAP in nature. The obtained results revealed that β-CD complexation is more suitable for vitamin A than other two types vitamin A esters in promoting thermal stability and water solubility. On the basis of these experimental studies, we furthermore performed molecular docking simulations to predict possible binding mode and binding affinities of three vitamins with β-CDs. Gibbs free energy changes (ΔG°) of β-CD:VA with 2:1 molecular ratio was lowest, which inducing the thermal stability of VA was tremendously enhanced than VAA and VAP, that was powerfully supported by molecular docking simulation. It was great significant for the enlarged application of the β-CD: vitamin A/ vitamin A esters inclusion complexes.