载五味子乙素F127修饰脂质聚合物纳米粒抑制乳腺癌肺转移的研究

Preparation and evaluation of schisandrin B-loaded F127 modified lipid-polymer nanoparticles for inhibition of breast cancer lung metastasis

构建载五味子乙素(schisandrin B,SchB)F127修饰脂质聚合物纳米粒(SchB-F-LPNs),增强SchB抑制乳腺癌转移的作用。采用改良的纳米沉淀法制备纳米粒。SchB-F-LPNs形态圆整,具有壳核结构,平均粒径为(234.60±6.11)nm,Zeta电位为(-5.88±0.49)mV。XRD分析结果表明SchB以无定形状态存在于脂质聚合物纳米粒中。F-LPNs体外猪黏液层穿越表观渗透系数是LPNs的1.43倍。大鼠口服体内药动学研究结果表明SchB混悬剂组、SchB-LPNs组和SchB-F-LPNs组Cmax分别为(369.06±146.94),(1121.34±91.65),(2951.91±360.53)μg·L^-1,以SchB混悬剂为参比制剂,SchB-F-LPNs的相对口服生物利用度为568.60%。SchB-F-LPNs可抑制在转化生长因子-β1(transforming growth factor-β1,TGF-β1)诱导下乳腺癌4T1细胞上皮间质转化产生的形态变化。此外,SchB-F-LPNs可显著降低4T1荷瘤小鼠肺转移结节数,揭示其具有抑制乳腺癌肺转移的作用。SchB-F-LPNs在抑制乳腺癌肺转移方面可能具有良好的潜力和应用前景。

In the current study,schisandrin B(SchB)-loaded F127 modified lipid-polymer hybrid nanoparticles(SchB-F-LPNs)were developed to improve the inhibition of breast cancer lung metastasis.Modified nanoprecipitation method was used to prepare SchB-F-LPNs.The nanoparticles were spherical in shape with shell-core structure by TEM observation.SchB-F-LPNs showed a mean particle size of(234.60±6.11)nm with zeta potential of(-5.88±0.49)mV.XRD results indicated that SchB existed in the nanoparticles in an amorphous state.The apparent permeability coefficient through porcine mucus of F-LPNs was 1.43-fold of that of LPNs as shown in the in vitro mucus penetration study.The pharmacokinetics study showed that the Cmax of SchB was(369.06±146.94)μg·L^-1,(1121.34±91.65)μg·L^-1 and(2951.91±360.53)μg·L^-1 respectively in SchB suspensions group,SchB-LPNs group and SchB-F-LPNs group after oral administration in rats.With SchB suspensions as the reference formulation,the relative bioavailability of SchB-F-LPNs was 568.60%.SchB-F-LPNs inhibited the morphological change during transforming growth factor-β1(TGF-β1)-induced epithelial-mesenchymal transition.In addition,SchB-F-LPNs significantly decreased the number of metastatic pulmonary nodules in 4 T1 tumor-bearing mice,suggesting that SchB-F-LPNs may inhibit the metastasis of breast cancer.These results reveal the promising potential of SchB-F-LPNs in treatment of breast cancer lung metastasis.