Institute of Life Sciences, Jilin University, Changchun, Jilin, China.
Int J Pharm. 2013 Jun 25;450(1-2):250-8. doi: 10.1016/j.ijpharm.2013.04.065. Epub 2013 Apr 27.
The Ginsenoside Rg3 has been shown to possess antiangiogenic and anticancer properties. Because of its limited water solubility, we decided to design and synthesize liposomal Rg3 (L-Rg3), to optimize preparation conditions, and to investigate further whether liposome could enhance the anticancer activity of Rg3. L-Rg3 was prepared using a film-dispersion method and the preparation conditions were optimized with response surface methodology (RSM). The mean encapsulation efficiency (EE) of 82.47% was close to the predicted value of 89.69%. Therefore, the optimized preparation condition was predicted correctly. We evaluated the cytotoxicity, pharmacokinetics, biodistribution and antitumor activities of L-Rg3. HepG2 and A549 cells were treated with Rg3 or L-Rg3 at different concentrations in vitro. Pharmacokinetics and biodistribution studies were carried out in Wistar rats. Tumor model was established by inoculating a suspension of A549 cells into BALB/c nude mice. The mice were divided into Saline, Rg3 solution, and L-Rg3 groups with the drug given by i.p. injection. Survival of the mice and tumor volume were monitored. In addition, CD34 immunohistochemical analysis was used for measuring microvessel density (MVD) of the tumor tissues. The cytotoxicity and ratio of tumor inhibition of L-Rg3 group were significantly higher than the Rg3 solution group. MVD values in the Rg3 solution and L-Rg3 groups decreased, especially in the L-Rg3 group. Compared to Rg3 solution, the L-Rg3 showed increased Cmax and AUC of Rg3 by 1.19- and 1.52-fold, respectively. This liposomal formulation could potentially produce a viable clinical agent for improving the anticancer activity of Rg3.
人参皂苷 Rg3 已被证明具有抗血管生成和抗癌特性。由于其水溶性有限，我们决定设计并合成脂质体 Rg3（L-Rg3），以优化制备条件，并进一步研究脂质体是否能增强 Rg3 的抗癌活性。L-Rg3 采用薄膜分散法制备，并采用响应面法（RSM）优化了制备条件。 82.47%的平均包封效率（EE）接近 89.69%的预测值。因此，优化的制备条件得到了正确预测。我们评估了 L-Rg3 的细胞毒性、药代动力学、生物分布和抗肿瘤活性。 HepG2 和 A549 细胞在体外用 Rg3 或 L-Rg3 不同浓度处理。在 Wistar 大鼠中进行药代动力学和生物分布研究。通过向 BALB/c 裸鼠接种 A549 细胞悬浮液建立肿瘤模型。将小鼠分为生理盐水、Rg3 溶液和 L-Rg3 组，通过腹腔注射给予药物。监测小鼠的存活和肿瘤体积。此外，采用 CD34 免疫组织化学分析测量肿瘤组织的微血管密度（MVD）。 L-Rg3 组的细胞毒性和肿瘤抑制率明显高于 Rg3 溶液组。 Rg3 溶液和 L-Rg3 组的 MVD 值降低，尤其是 L-Rg3 组。与 Rg3 溶液相比，L-Rg3 使 Rg3 的 Cmax 和 AUC 分别增加了 1.19 倍和 1.52 倍。这种脂质体制剂有可能成为一种可行的临床制剂，以提高 Rg3 的抗癌活性。
