Characterization and evaluation of inclusion complexes between astaxanthin esters with different molecular structures and hydroxypropyl-β-cyclodextrin

摘要

In this study, we focused on the characterization and evaluation of the inclusion complexes between astaxanthin esters (Asta-E) and hydroxypropyl-beta-cyclodextrin (HP beta-CD). Asta-E of varying chain lengths (C4, C8, C18, and C22) and unsaturation degrees (C22:0 and C22:6) of the fatty acids were purified, and the inclusion complexes of HP beta-CD with Asta-E were characterized by various methods (phase solubility analysis, differential scanning calorimetry, ultraviolet-visible absorption spectroscopy, Fourier-transform infrared spectroscopy, and H-1 nuclear magnetic resonance spectrometry). Thermodynamic analyses showed that astaxanthin docosahexaenoic acid monoester (Asta-C22:6) had the best binding capacity among the HP beta-CD-Asta-E inclusion complexes (complexation efficiency was 14.42 x 10(-3) at 310 K). Moreover, binding site analysis of Asta-E with HP beta-CD indicated that the six-membered Asta-E ring was bound in the cavity of HP beta-CD by hydrogen bonds. The fatty acid chain had a positive influence on both the thermal stability and binding capacity of the inclusion complexes. Asta-C22:6 was selected to investigate the enhancing effect HP beta-CD has on its anticancer activity, oral bioavailability, and storage stability. HP beta-CD-Asta-C22:6 inclusion complex exhibited higher antiproliferative activity on HepG2 cells (IC50 = 160 mu g/mL for 48 h) and arrested the cells in their S and G2/M phases. Bioavailability experiments showed that the area under curve (AUC(0-t)) after oral gavage of the HPP-CD-AstaC22:6 inclusion complex (9.62 + 0.21 h mu g/mL) was 2.68-times higher than that after oral gavage of Asta-C22:6 (3.59 + 0.33 h mu g/mL). Thus, the formation of an inclusion complex with HP beta-CD is an effective method to solubilize and stabilize Asta-E for potential future applications.