Abstract In this study, we focused on the characterization and evaluation of the inclusion complexes between astaxanthin esters (Asta-E) and hydroxypropyl-β-cyclodextrin (HPβ-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 HPβ-CD with Asta-E were characterized by various methods (phase solubility analysis, differential scanning calorimetry, ultraviolet–visible absorption spectroscopy, Fourier-transform infrared spectroscopy, and 1H nuclear magnetic resonance spectrometry). Thermodynamic analyses showed that astaxanthin docosahexaenoic acid monoester (Asta-C22:6) had the best binding capacity among the HPβ-CD–Asta-E inclusion complexes (complexation efficiency was 14.42 × 10⁻3 at 310 K). Moreover, binding site analysis of Asta-E with HPβ-CD indicated that the six-membered Asta-E ring was bound in the cavity of HPβ-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 HPβ-CD has on its anticancer activity, oral bioavailability, and storage stability. HPβ-CD–Asta-C22:6 inclusion complex exhibited higher antiproliferative activity on HepG2 cells (IC50 = 160 μg/mL for 48 h) and arrested the cells in their S and G2/M phases. Bioavailability experiments showed that the area under curve (AUC0–t) after oral gavage of the HPβ-CD−Asta-C22:6 inclusion complex (9.62 ± 0.21 h μg/mL) was 2.68-times higher than that after oral gavage of Asta-C22:6 (3.59 ± 0.33 h μg/mL). Thus, the formation of an inclusion complex with HPβ-CD is an effective method to solubilize and stabilize Asta-E for potential future applications.

中文翻译：

---

不同分子结构虾青素酯与羟丙基-β-环糊精包合物的表征与评价

摘要 在这项研究中，我们专注于虾青素酯 (Asta-E) 和羟丙基-β-环糊精 (HPβ-CD) 之间的包合物的表征和评估。纯化不同链长（C4、C8、C18 和 C22）和不饱和度（C22:0 和 C22:6）脂肪酸的 Asta-E，表征 HPβ-CD 与 Asta-E 的包合物通过各种方法（相溶解度分析、差示扫描量热法、紫外-可见吸收光谱、傅里叶变换红外光谱和 1H 核磁共振光谱）。热力学分析表明，虾青素二十二碳六烯酸单酯 (Asta-C22:6) 在 HPβ-CD-Asta-E 包合物中具有最好的结合能力（310 K 时的络合效率为 14.42 × 10⁻3）。而且，Asta-E 与 HPβ-CD 的结合位点分析表明，六元 Asta-E 环通过氢键结合在 HPβ-CD 的空腔中。脂肪酸链对包合物的热稳定性和结合能力都有积极的影响。选择 Asta-C22:6 来研究 HPβ-CD 对其抗癌活性、口服生物利用度和储存稳定性的增强作用。HPβ-CD-Asta-C22:6 包合物对 HepG2 细胞表现出更高的抗增殖活性（IC50 = 160 μg/mL，持续 48 小时）并将细胞阻滞在 S 期和 G2/M 期。生物利用度实验表明，HPβ-CD-Asta-C22:6 包合物（9.62 ± 0.21 h μg/mL）经口管饲后的曲线下面积（AUC0-t）是 Asta 管饲后的 2.68 倍-C22:6 (3.59 ± 0.33 h μg/mL)。因此，