Folic acid-modified nonionic surfactant vesicles for gambogenic acid targeting: Preparation, characterization, and in vitro and in vivo evaluation
Folic acid-modified nonionic surfactant vesicles for gambogenic acid targeting: Preparation, characterization, and in vitro and in vivo evaluation
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DOI：
10.1002/kjm2.12162
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发表时间：
2020-04-15
影响因子：
3.3
通讯作者：
Chen, Wei-Dong
中科院分区：
文献类型：
--
作者：
Lin, Tong-Yuan;Chang, Jia-Li;Chen, Wei-Dong
本研究的目的是开发叶酸（FA）修饰的非离子表面活性剂囊泡（NISVs，囊泡）作为载体系统的靶向输送藤黄酸（GNA）。FA-GNA-NISV表现出180.77 +/-2.41 nm的平均粒度，通过动态光散射测定的窄聚分散指数为0.147 +/-0.08。透射电子显微镜也显示FA-GNA-NISVs为具有双层结构的球形。最佳FA-GNA-NISV的包封效率（EE%）和ζ电位分别为87.84 +/- 1.06%和-37.33 +/- 0.33 mV。差示扫描量热法显示FA-NISVs内GNA以分子或无定形状态存在，体外释放曲线表明FA-GNA-NISVs可持续释放GNA，透析12小时内FA-NISVs释放的GNA不到60%。体内药代动力学结果表明，FA-GNA-NISV在肺中具有相当高的C-max、曲线下面积（AUC（0 - t））和蓄积。细胞增殖研究表明，FA-GNA-NISV显著增强了对A549细胞的体外细胞毒性。流式细胞术和荧光显微镜进一步证明，与未修饰的GNA-NISV和游离GNA相比，FA-GNA-NISV增加了细胞凋亡。此外，FA-GNA-NISVs以剂量依赖性方式诱导A549细胞凋亡。此外，细胞摄取测定显示FA-GNA-NISV的摄取高于GNA-NISV以及游离GNA。综上所述，可以得出结论，FA-GNA-NISV被提出作为一种新的靶向载体，用于将GNA有效地递送到癌细胞。
The aim of present study was to develop folic acid (FA)-modified nonionic surfactant vesicles (NISVs, niosomes) as carrier systems for targeted delivery of gambogenic acid (GNA). The FA-GNA-NISVs exhibited a mean particle size of 180.77 +/- 2.41 nm with a narrow poly dispersion index of 0.147 +/- 0.08 determined by dynamic light scattering. Transmission electron microscopy also revealed that the FA-GNA-NISVs were spherical with double-layer structure. Entrapment efficiency (EE%) and zeta potential of the optimal FA-GNA-NISVs were 87.84 +/- 1.06% and -37.33 +/- 0.33 mV, respectively. Differential scanning calorimetry demonstrated that the GNA was in a molecular or amorphous state inside the FA-NISVs in vitro release profiles suggested that FA-GNA-NISVs could release GNA at a sustained manner, and less than 60% of GNA was released from the FA-NISVs within 12 hours of dialysis. in vivo pharmacokinetic results illustrated that FA-GNA-NISVs had considerably higher C-max, area under curve (AUC(0 - t)) and accumulation in lung. The cell proliferation study shown that the FA-GNA-NISVs significantly enhanced the in vitro cytotoxicity against A549 cells. Flow cytometry and fluorescence microscopy further demonstrated that the FA-GNA-NISVs increased apoptosis compared with nonmodified GNA-NISVs and free GNA. Moreover, FA-GNA-NISVs induced A549 cell apoptosis in a dose-dependent manner. In addition, cellular uptake assays showed a higher uptake of FA-GNA-NISVs than GNA-NISVs as well as free GNA. Taken together, it could be concluded that FA-GNA-NISVs were proposed as a novel targeting carriers for efficient delivering of GNA to cancers cells.