Purpose

Silybin (SB) is the most potent flavonolignan extracted from the milk thistle plant, showing anti-oxidative properties. Owing to the lipophilic nature of SB, the oral bioavailability of SB is low. This study developed and optimized SB loaded solid lipid nanoparticles (SB-SLNs), and evaluated their in vitro and in vivo characteristics.

Methods

The applied method of SLNs production was solvent emulsification and evaporation, using stearic acid as the solid lipid core and Cremophor® RH40 as the surfactant. The statistical optimization was determined using Box-Behnken design. The morphology of the optimized silybin-loaded SLNs was detected by scanning electron microscopy. Also, differential scanning calorimetry (DSC), Fourier transformation infrared spectroscopy (FTIR), and powder X-ray diffractometry (P-XRD) were used to characterize SLNs’ physicochemical properties. Moreover, in vivo studies for pharmacokinetic properties of SB were performed on male Wistar rats.

Results

The optimum formulation exhibited the size of 262.36 ± 12 nm, and -22.22 ± 0.87 mV of zeta potential and 74.02 ± 1.66% of entrapment efficiency. The scanning electron microscopy(SEM) images demonstrated the rough-surfaced ovate structure of SB-SLNs, and solid-state research evince the amorphous state of SB-SLNs. The in vivo evaluations showed an increased bioavailability of SLN formulation higher than pure SB in plasma.

Conclusion

The significant improvement of SB-SLNs pharmacokinetic properties after single oral dose administration specified SLNs as a capable drug delivery system for SB.

中文翻译：

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通过 Box-Behnken 设计系统优化水飞蓟宾固体脂质纳米颗粒以改善口服药物递送：体外和体内评估

目的

水飞蓟宾 (SB) 是从奶蓟植物中提取的最有效的黄酮木脂素，具有抗氧化特性。由于 SB 的亲脂性，SB 的口服生物利用度较低。本研究开发和优化了负载 SB 的固体脂质纳米颗粒 (SB-SLN)，并评估了它们的体外和体内特性。

方法

SLNs生产的应用方法是溶剂乳化和蒸发，使用硬脂酸作为固体脂质核心，Cremophor® RH40作为表面活性剂。使用 Box-Behnken 设计确定统计优化。通过扫描电子显微镜检测优化的负载水飞蓟宾的 SLNs 的形态。此外，还采用差示扫描量热法 (DSC)、傅里叶变换红外光谱法 (FTIR) 和粉末 X 射线衍射法 (P-XRD) 来表征 SLNs 的物理化学性质。此外，对雄性 Wistar 大鼠进行了 SB 药代动力学特性的体内研究。

结果

最佳配方的尺寸为 262.36 ± 12 nm，zeta 电位为 -22.22 ± 0.87 mV，包埋效率为 74.02 ± 1.66%。扫描电子显微镜 (SEM) 图像显示了 SB-SLNs 的粗糙表面卵形结构, 固态研究表明 SB-SLNs 的非晶态。体内评估显示，血浆中 SLN 制剂的生物利用度高于纯 SB。

结论

单次口服给药后 SB-SLNs 药代动力学特性的显着改善使 SLNs 成为 SB 的有效药物递送系统。