Triptolide (TP), a broad-spectrum antitumor drug, has very poor solubility and oral bioavailability, which limits its clinical use. Compared with conventional formulations of TP, a casein (Cas)-based drug delivery system has been reported to have significant advantages for the improvement of solubility and bioavailability of insoluble drugs. In this paper, we report the successful preparation of TP-loaded Cas nanoparticles (TP-Cas) using the self-assembly characteristics of Cas in water and the optimization of the formulation by evaluation of entrapment efficiency (EE) and loading efficiency (LE). Dynamic light scattering, transmission electron microscopy, Fourier-transform infrared spectrometry, X-ray diffractometry (XRD), and differential scanning calorimetry (DSC) was adopted to characterize the TP-Cas. Results showed that the obtained TP-Cas were approximately spherical with a particle size of 128.7 ± 11.5 nm, EE of 72.7 ± 4.7 %, and LE of 8.0% ± 0.5%. Furthermore, in vitro release behavior of TP-Cas in PBS (pH = 7.4) was also evaluated, showing a sustained-release profile. Additionally, an in vivo study in rats displayed that the mean plasma concentration of TP after oral administration of TP-Cas was significantly higher than that treated with TP oral suspension. The C _max value for TP-Cas (8.0 ± 4.4 μg/mL) was significantly increased compared with the free TP (0.9 ± 0.3 μg/mL). Accordingly, the area under the curve (AUC_0-8) of TP-Cas was 2.8 ± 0.8 mg/L·h, 4.3-fold higher than that of TP suspension (0.6 ± 0.1 mg/L·h). Therefore, it can be concluded that TP-Cas enhanced the absorption and improved oral bioavailability of TP. Taking the good oral safety of Cas into consideration, TP-Cas should be a more promising preparation of TP for clinical application.

雷公藤内酯醇（TP）是一种广谱抗肿瘤药物，溶解度和口服生物利用度非常差，限制了其临床应用。与传统的TP制剂相比，基于酪蛋白（Cas）的药物递送系统据报道在改善不溶性药物的溶解度和生物利用度方面具有显着优势。在本文中，我们报道了利用Cas在水中的自组装特性成功制备了TP负载的Cas纳米颗粒（TP-Cas），并通过评估包封率（EE）和负载效率（LE）对配方进行了优化。采用动态光散射，透射电子显微镜，傅立叶变换红外光谱，X射线衍射法（XRD）和差示扫描量热法（DSC）表征TP-Cas。结果表明，所得TP-Cas为近似球形，粒径为128.7±11.5nm，EE为72.7±4.7％，LE为8.0％±0.5％。此外，还评估了TP-Cas在PBS（pH = 7.4）中的体外释放行为，显示了持续释放曲线。另外，在大鼠中的一项体内研究显示，口服TP-Cas后，TP的平均血浆浓度显着高于用TP口服混悬剂治疗的血浆平均浓度。的 在大鼠体内进行的一项研究显示，口服TP-Cas后，TP的平均血浆浓度显着高于TP口服混悬剂治疗的血浆平均浓度。的 在大鼠体内进行的一项研究显示，口服TP-Cas后，TP的平均血浆浓度显着高于TP口服混悬剂治疗的血浆平均浓度。的 与游离TP（0.9±0.3μg/ mL）相比，TP-Cas的C_最大值（8.0±4.4μg/ mL）显着增加。因此，TP-Cas的曲线下面积（AUC _0-8）为2.8±0.8mg / L·h，比TP悬浮液（0.6±0.1mg / L·h）高4.3倍。因此，可以得出结论，TP-Cas增强了TP的吸收并改善了其口服生物利用度。考虑到Cas的良好口服安全性，TP-Cas应该是临床上更有希望的TP制剂。