Xia Na, Zhou Qian, Liu Yanquan, Gao Dan, Zhu Siming, Feng Zuoshan
Key Laboratory of Biological Resources and Ecology of Pamirs Plateau of Xinjiang, College of Life and Geographic Sciences, Kashi University, Kashi 844000, China.
School of Food Science and Engineering, South China University of Technology, Guangzhou 510641, China.
Nanomaterials (Basel). 2025 Jun 3;15(11):862. doi: 10.3390/nano15110862.
Neohesperidin (NH), a bioactive flavanone glycoside, exhibits multifaceted pharmacological properties including antioxidant and anti-inflammatory activities. However, its clinical application is severely constrained by inherent physicochemical limitations such as poor aqueous solubility and instability under physiological conditions. To address these challenges, this study developed a dual-carrier nano-liposomal system through the synergistic integration of phospholipid complexation and hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion technologies. Two formulations-NH-PC (phospholipid complex) and NH-PC-CD (phospholipid/HP-β-CD hybrid)-were fabricated via ultrasonication-assisted ethanol precipitation. Comprehensive characterization using FTIR and PXRD confirmed the amorphous dispersion of NH within lipid bilayers, with complete elimination of crystalline diffraction peaks, indicative of molecular-level interactions between NH's hydroxyl groups and phospholipid polar moieties. The engineered nanosystems demonstrated remarkable solubility enhancement, achieving 321.77 μg/mL (NH-PC) and 318.75 μg/mL (NH-PC-CD), representing 2.01- and 1.99-fold increases over free NH. Encapsulation efficiencies exceeded 95% for both formulations, with sustained release profiles revealing 60.81% (NH-PC) and 80.78% (NH-PC-CD) cumulative release over 72 h, governed predominantly by non-Fickian diffusion kinetics. In vitro gastrointestinal simulations highlighted superior bioaccessibility for NH-PC-CD (66.35%) compared to NH-PC (58.52%) and free NH (20.85%), attributed to enhanced stability against enzymatic degradation. Storage stability assessments further validated the robustness of HP-β-CD-modified liposomes, with NH-PC-CD maintaining consistent particle size (<3% variation) and encapsulation efficiency (>92%) over 30 days. Antioxidant evaluations demonstrated concentration-dependent DPPH radical scavenging, wherein nanoencapsulation significantly amplified NH's activity compared to its free form. This study establishes a paradigm for dual-functional nanocarriers, offering a scalable strategy to optimize the delivery of hydrophobic nutraceuticals while addressing critical challenges in bioavailability and physiological stability.
新橙皮苷（NH）是一种具有生物活性的黄酮醇苷，具有多方面的药理特性，包括抗氧化和抗炎活性。然而，其临床应用受到固有物理化学限制的严重制约，如在生理条件下水溶性差和稳定性不佳。为应对这些挑战，本研究通过磷脂络合和羟丙基-β-环糊精（HP-β-CD）包合技术的协同整合，开发了一种双载体纳米脂质体系统。通过超声辅助乙醇沉淀法制备了两种制剂——NH-PC（磷脂复合物）和NH-PC-CD（磷脂/HP-β-CD杂化物）。利用傅里叶变换红外光谱（FTIR）和粉末X射线衍射（PXRD）进行的全面表征证实了NH在脂质双层中的无定形分散，结晶衍射峰完全消失，这表明NH的羟基与磷脂极性部分之间存在分子水平的相互作用。所构建的纳米系统显示出显著的溶解度提高，NH-PC达到321.77μg/mL，NH-PC-CD达到318.75μg/mL，分别比游离NH增加了2.01倍和1.99倍。两种制剂的包封率均超过95%，缓释曲线显示在72小时内累积释放率分别为60.81%（NH-PC）和80.78%（NH-PC-CD），主要受非菲克扩散动力学控制。体外胃肠道模拟实验表明，与NH-PC（58.52%）和游离NH（20.85%）相比，NH-PC-CD具有更高的生物可及性（66.35%），这归因于其对酶降解的稳定性增强。储存稳定性评估进一步验证了HP-β-CD修饰脂质体的稳定性，NH-PC-CD在30天内保持一致的粒径（变化<3%）和包封率（>92%）。抗氧化评估表明，纳米包封的NH具有浓度依赖性的DPPH自由基清除能力，与游离形式相比，纳米包封显著增强了NH的活性。本研究建立了一种双功能纳米载体的范例，提供了一种可扩展的策略，以优化疏水性营养保健品的递送，同时解决生物利用度和生理稳定性方面的关键挑战。
