Cytogenetics and Molecular Biology Laboratory, Department of Zoology, University of Kalyani, Kalyani 741 235, India.
Eur J Pharm Sci. 2012 Sep 29;47(2):313-24. doi: 10.1016/j.ejps.2012.06.018. Epub 2012 Jul 6.
We tested relative efficacy of the extract of Phytolacca decandra (PD) and its PLGA nano-encapsulated form (NPD) in mice intoxicated with benzo[a]pyrene (BaP) (25 mg/kg b.w.) plus sodium-arsenite (SA) (10 mg/kg b.w.) and on A549 lung cancer cells in vitro. We characterized nanoparticles by physico-chemical and morphological studies using dynamic light scattering, scanning electron and atomic force microscopies. We also conducted FTIR and (1)H NMR studies to determine if NPD had a co-polymeric nature and analyzed drug-DNA interaction through circular dichroism spectra (CD) and melting temperature profiles (T(m)) taking calf thymus DNA as target. An oral dose of 0.3mg/kg b.w. for NPD and 30 mg/kg b.w. for PD in mice showed chemopreventive effects in regard to DNA fragmentation, comet tail length and toxicity biomarkers like ROS generation, NFκβ, p53, PARP, CYP1A1 and caspase 3. NPD showed greater effects than that by PD. Results of in vivo studies showed similar effects on A549 in regard to cell viability, DAPI and PI staining, Comet tail length, DNA fragmentation. To further confirm the biological molecule present in PD we analyzed its chromatographic fraction through mass spectroscopy, NMR and FT-IR studies and characterized it to be a tri-terpenoid, a derivative of betulinic acid with a molecular formula C(30)H(46)O(2.) Thus, overall results suggest that nano-encapsulation of PD (NPD) increases drug bioavailability and thereby has a better chemo-preventive action against lung cancer in vivo and on A549 cells in vitro than that of PD.
我们测试了垂序商陆（PD）提取物及其 PLGA 纳米囊泡形式（NPD）在苯并[a]芘（BaP）（25mg/kg b.w.）加亚砷酸钠（SA）（10mg/kg b.w.）诱导的小鼠中毒模型和体外 A549 肺癌细胞中的相对疗效。我们通过动态光散射、扫描电子显微镜和原子力显微镜等物理化学和形态学研究对纳米颗粒进行了表征。我们还进行了傅里叶变换红外光谱（FTIR）和（1）H 核磁共振（NMR）研究，以确定 NPD 是否具有共聚物性质，并通过圆二色光谱（CD）和熔点（T（m））分析药物-DNA 相互作用，以小牛胸腺 DNA 为靶标。NPD 给小鼠口服 0.3mg/kg b.w.，PD 给小鼠口服 30mg/kg b.w.，在 DNA 片段化、彗星尾长和毒性生物标志物如 ROS 生成、NFκβ、p53、PARP、CYP1A1 和 caspase 3 方面显示出化学预防作用。NPD 的效果大于 PD。体内研究结果显示，在 A549 细胞活力、DAPI 和 PI 染色、彗星尾长、DNA 片段化方面，NPD 表现出相似的作用。为了进一步证实 PD 中的生物分子，我们通过质谱、NMR 和 FT-IR 研究分析了其色谱馏分，并将其鉴定为三萜类化合物，是白桦脂酸的衍生物，分子式为 C(30)H(46)O(2)。因此，总体结果表明，PD 的纳米囊泡化（NPD）增加了药物的生物利用度，从而在体内对肺癌和体外对 A549 细胞具有比 PD 更好的化学预防作用。
