Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Peking University, Beijing 100191, China.
Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
J Biomed Nanotechnol. 2021 May 1;17(5):942-951. doi: 10.1166/jbn.2021.3077.
Naringenin (NGN) can be used to inhibit the progression of nonalcoholic fatty liver disease (NAFLD) in mice, but its poor water solubility limits its applications. Nanostructured lipid carriers (NLCs) have recently attracted much attention in the field of nanodrug delivery systems because they increase the drug loading capacity and impressively enhance the solubility of indissolvable drugs. Herein, a thin-film dispersion method was used to prepare naringenin-loaded nanostructured lipid carriers (NGN-NLCs). These NGN-NLCs have a narrow size distribution of 171.9 ±2.0 nm, a high drug loading capacity of 23.7 ± 0.3%, a high encapsulation efficiency of 99.9 ± 0.0% and a drug release rate of 86.2 ± 0.4%. NGN- NLCs elevated the pharmacokinetic parameters (C and AUC) of NGN, accelerated NGN transepithelial transport in MDCK cells and intestinal absorption in the jejunum and ileum, and reduced hepatic lipid accumulation in an oleic acid (OA) plus lipopolysaccharide (LPS)-induced lipid deposition cell model in primary hepatocytes and in a methionine/choline deficient (MCD) diet-induced NAFLD mouse model. A detailed study of the mechanism showed that this NLC formulation elevated the drug release rate in simulated intestinal solutions the transepithelial transport in MDCK cells, the oral absorption in mice and the intestinal absorption of NGN. Thus, NGN-NLCs significantly enhanced the inhibitory effects of NGN on MCD diet induced mouse NAFLD.
柚皮素（NGN）可用于抑制非酒精性脂肪性肝病（NAFLD）在小鼠中的进展，但由于其水溶性差，限制了其应用。纳米结构脂质载体（NLCs）最近在纳米药物传递系统领域引起了广泛关注，因为它们增加了药物载药量，并显著提高了难溶性药物的溶解度。在此，采用薄膜分散法制备了柚皮素载纳米结构脂质载体（NGN-NLCs）。这些 NGN-NLCs 的粒径分布窄，为 171.9±2.0nm，载药量高，为 23.7±0.3%，包封率高，为 99.9±0.0%，药物释放率为 86.2±0.4%。NGN-NLCs 提高了 NGN 的药代动力学参数（C 和 AUC），加速了 NGN 在 MDCK 细胞中的跨上皮转运以及在空肠和回肠中的肠吸收，并减少了油酸（OA）加脂多糖（LPS）诱导的原代肝细胞和蛋氨酸/胆碱缺乏（MCD）饮食诱导的 NAFLD 小鼠模型中的肝脂质积累。对机制的详细研究表明，这种 NLC 制剂提高了模拟肠液中的药物释放率，促进了 MDCK 细胞中的跨上皮转运，提高了小鼠的口服吸收和 NGN 的肠吸收。因此，NGN-NLCs 显著增强了 NGN 对 MCD 饮食诱导的 NAFLD 小鼠的抑制作用。
