Formulation, characterization, and geno/cytotoxicity studies of galbanic acid-loaded solid lipid nanoparticles
Formulation, characterization, and geno/cytotoxicity studies of galbanic acid-loaded solid lipid nanoparticles
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DOI：
10.3109/13880209.2014.991836
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发表时间：
2015-01-01
影响因子：
3.8
通讯作者：
Nazemiyeh, Hossein
中科院分区：
文献类型：
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作者：
Eskandani, Morteza;Barar, Jaleh;Nazemiyeh, Hossein
背景：加巴尼酸(GBA)是一种倍半萜香豆素，具有不同的药理作用和抗癌作用。目的：为提高GBA的抗癌活性，本研究旨在制备GBA固体脂质纳米粒(GBA-SLNS)，并研究其体外生物活性。测定包封率(EE)、载药量(DL)和体外释放度。采用四甲基偶氮唑盐比色法、DNA片段化试验、彗星试验和Anexin V细胞凋亡试验比较GBA和GBA-SLNS对A549细胞和HUVEC的抗细胞增殖和遗传毒性作用，检测作用48h后细胞的凋亡率和DNA损伤情况。结果：扫描电子显微镜和粒度分析显示SLN呈球形(92 Nm)，分布均匀，Zeta电位为-23.39 mV。获得了较高的EE(>；98%)和较长的体外释放。3个月后，GBA-SLNS在水介质中的尺寸和多分散性指数得到了证实。GBA能抑制A549细胞的生长，48h的IC50值为62mU M。虽然GBA-SLNS也能抑制A549细胞的生长，但48h后BclxL和Casp 9基因的定量表达以及遗传毒性分析证实了GBA-SLNS的作用。结论：与GBA相比，GBA-SLNS具有长期的凋亡作用，可能是由于肿瘤病理变化导致GBA-SLNS在肿瘤部位蓄积。我们的数据证实，SLNS可以用于持续的亲脂性GBA递送。
Context: Galbanic acid (GBA) is a sesquiterpene coumarin with different medicinal properties and anticancer effects.Objective: To improve the anticancer activities of GBA, in the current study, we aimed to fabricate GBA-loaded solid lipid nanoparticles (GBA-SLNs) and study their biological activities in vitro.Materials and methods: Hot homogenization was used for preparation of GBA-SLNs. The encapsulation efficiency (EE) and drug loading (DL) and in vitro release were determined. MTT, DAPI, DNA fragmentation, comet, and Anexin V apoptosis assays were used to compare the anti-cell proliferation and genotoxicity properties of GBA and GBA-SLNs against A549 cells and HUVEC to detect apoptosis and DNA damage in the final concentration of 100 mu M after 48 h treatment.Results: Scanning electron microscopy (SEM) and particle size analysis showed spherical SLNs (92 nm), monodispersed distribution, and zeta potential of -23.39 mV. High EE (>98%) and long-term in vitro release were achieved. The stability of GBA-SLNs in aqueous medium was approved after 3 months in terms of size and polydispersity index. GBA was able to inhibit A549 growth with an IC50 value of 62 mu M at 48 h. Although GBA-SLNs could also inhibit the growth rate of A549 cells, the effect is perceived after 48 h, as approved by the quantitative expression of Bcl-xL and Casp 9 genes, and also genotoxicity assays.Conclusion: Long-term apoptotic effect of GBA-SLNs compared with GBA may be due to the accumulation of GBA-SLNs in the tumor site because of deviant tumor pathology. Our data confirmed that SLNs could be exploited for sustained lipophilic GBA delivery.