Dr B.R. Ambedkar Centre for Biomedical Research, University of Delhi, Delhi.
Anticancer Drugs. 2011 Jul;22(6):543-55. doi: 10.1097/CAD.0b013e32834159b8.
Noscapine, the tubulin-binding anticancer agent, when administered orally, requires high ED(50) (300-600 mg/kg), whereas intravenous administration (10 mg/kg) results in rapid elimination of the drug with a half-life of 0.39 h. Hence, the development of long-circulating injectable nanoparticles can be an interesting option for designing a viable formulation of noscapine for anticancer activity. Noscapine-enveloped gelatin nanoparticles and poly(ethylene glycol)-grafted gelatin nanoparticles were constructed and characterized. Data indicate that smooth and spherical shaped nanoparticles of 127 ± 15 nm were engineered with maximum entrapment efficiency of 65.32 ± 3.81%. Circular dichroism confirms that nanocoacervates retained the α-helical content of gelatin in ethanol whereas acetone favored the formation of a random coil. Moreover, the Fourier transform infrared and powder X-ray diffraction pattern prevents any significant change in the noscapine-loaded gelatin nanoparticles in comparison with individual components. In-vitro release kinetic data suggest a first-order release of noscapine (85.1%) from gelatin nanoparticles with a release rate constant of 7.611×10(-3). It is to be noted that there is a 1.43-fold increase in the area under the curve up to the last sampling point for the noscapine-loaded poly(ethylene glycol)-grafted gelatin nanoparticles over the noscapine-loaded gelatin nanoparticles and a 13.09-fold increase over noscapine. Cytotoxicity analysis of the MCF-7 cell line indicated that the IC(50) value of the noscapine-loaded poly(ethylene glycol)-grafted gelatin nanoparticles was equivalent to 20.8 μmol/l, which was significantly (P<0.05) lower than the IC(50) value of the noscapine-loaded gelatin nanoparticles (26.3 μmol/l) and noscapine (40.5 μmol/l).Noscapine-loaded poly(ethylene glycol)-grafted gelatin nanoparticles can be developed as a promising therapeutic agent for the management of breast cancer.
纳库平是一种微管结合型抗癌药物，口服时需要高 ED（50）（300-600mg/kg），而静脉给药（10mg/kg）则导致药物迅速消除，半衰期为 0.39h。因此，开发长循环可注射纳米粒可以是设计用于抗癌活性的纳库平可行制剂的一个有趣选择。构建并表征了纳库平包封明胶纳米粒和聚乙二醇接枝明胶纳米粒。数据表明，工程化的纳米粒呈光滑的球形，粒径为 127±15nm，最大包封效率为 65.32±3.81%。圆二色性证实，纳米共聚物在乙醇中保留了明胶的α-螺旋结构，而在丙酮中有利于形成无规卷曲。此外，傅里叶变换红外和粉末 X 射线衍射图谱表明，与单个成分相比，载药明胶纳米粒没有发生任何显著变化。体外释放动力学数据表明，纳库平从明胶纳米粒中的释放符合一级动力学（85.1%），释放速率常数为 7.611×10（-3）。值得注意的是，与载药明胶纳米粒相比，载药聚乙二醇接枝明胶纳米粒的纳库平在最后一个取样点的曲线下面积增加了 1.43 倍，与纳库平相比增加了 13.09 倍。MCF-7 细胞系的细胞毒性分析表明，载药聚乙二醇接枝明胶纳米粒的纳库平 IC（50）值相当于 20.8μmol/L，显著低于载药明胶纳米粒（26.3μmol/L）和纳库平（40.5μmol/L）的纳库平 IC（50）值（P<0.05）。载药聚乙二醇接枝明胶纳米粒可作为治疗乳腺癌的有前途的治疗剂。
