Thymoquinone-loaded nanostructured lipid carriers: preparation, gastroprotection, in vitro toxicity, and pharmacokinetic properties after extravascular administration.
Thymoquinone-loaded nanostructured lipid carriers: preparation, gastroprotection, in vitro toxicity, and pharmacokinetic properties after extravascular administration.
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负载百里醌的纳米结构脂质载体：制备、胃保护、体外毒性和血管外给药后的药代动力学特性。
DOI：
10.2147/ijn.s44108
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发表时间：
2013
影响因子：
8
通讯作者：
Eid EE
中科院分区：
文献类型：
--
作者：
Abdelwahab SI;Sheikh BY;Taha MM;How CW;Abdullah R;Yagoub U;El-Sunousi R;Eid EE
纳米结构脂质载体（NLC）由固体和液体脂质以及表面活性剂组成，是潜在的良好胶体药物载体。百里醌是黑种草的主要生物活性成分。在这项研究中，制备，胃保护作用，和药物动力学（PK）特性的百里醌（TQ）负载的NLC（TQNLC）进行了评价。使用氢化棕榈油（Softisan® 154）、橄榄油和磷脂酰胆碱作为脂质相，使用山梨醇、聚山梨醇酯80、硫柳汞和双蒸水作为液体脂质材料，制备TQNLC。使用各种方法对TQNLC进行形态学评估。溃疡指数、氢浓度、粘液含量以及生物化学和组织化学研究的分析证实，将TQ加载到NLC中显著改善了这种天然化合物对乙醇诱导的溃疡形成的胃保护活性。以顺铂作为阳性对照，在WRL68肝正常细胞上测试TQNLC的安全性。TQNLC的平均直径为75 ± 2.4nm。这些颗粒的zeta电位值为-31 ± 0.1 mV，熔融峰为55.85 ° C。免疫组织化学方法显示，TQNLCs通过调节热休克蛋白70（Hsp70）抑制乙醇诱导的溃疡形成。在大鼠或正常人肝细胞中未观察到TQNLC的急性肝毒性作用（WRL-68）。经验证后，家兔PK研究表明TQ的PK特性得到改善，并表明药物表现为线性。TQ的Tmax、Cmax和消除半衰期分别为3.96 ± 0.19小时、4811.33 ± 55.52 ng/mL和4.4933 ± 0.015小时，表明TQ适用于血管外给药。NLCs可能是一种很有前途的口服TQ载体，并改善其胃保护特性。
Nanostructured lipid carriers (NLCs), composed of solid and liquid lipids, and surfactants are potentially good colloidal drug carriers. Thymoquinone is the main bioactive compound of Nigella sativa. In this study, the preparation, gastroprotective effects, and pharmacokinetic (PK) properties of thymoquinone (TQ)-loaded NLCs (TQNLCs) were evaluated. TQNLCs were prepared using hydrogenated palm oil (Softisan® 154), olive oil, and phosphatidylcholine for the lipid phase and sorbitol, polysorbate 80, thimerosal, and double distilled water for the liquid lipid material. A morphological assessment of TQNLCs was performed using various methods. Analysis of the ulcer index, hydrogen concentration, mucus content, and biochemical and histochemical studies confirmed that the loading of TQ into the NLCs significantly improved the gastroprotective activity of this natural compound against the formation of ethanol-induced ulcers. The safety of TQNLC was tested on WRL68 liver normal cells with cisplatin as a positive control. The average diameter of the TQNLCs was 75 ± 2.4 nm. The particles had negative zeta potential values of −31 ± 0.1 mV and a single melting peak of 55.85°C. Immunohistochemical methods revealed that TQNLCs inhibited the formation of ethanol-induced ulcers through the modulation of heat shock protein-70 (Hsp70). Acute hepatotoxic effects of the TQNLCs were not observed in rats or normal human liver cells (WRL-68). After validation, PK studies in rabbits showed that the PK properties of TQ were improved and indicated that the drug behaves linearly. The Tmax, Cmax, and elimination half-life of TQ were found to be 3.96 ± 0.19 hours, 4811.33 ± 55.52 ng/mL, and 4.4933 ± 0.015 hours, respectively, indicating that TQ is suitable for extravascular administration. NLCs could be a promising vehicle for the oral delivery of TQ and improve its gastroprotective properties.