Xu Lingyun, Chen Huabing, Xu Huibi, Yang Xiangliang
College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
Eur J Pharm Biopharm. 2008 Nov;70(3):741-8. doi: 10.1016/j.ejpb.2008.07.017. Epub 2008 Aug 13.
Triptolide (TP) possesses both anti-tumour and immuno-suppressive activities. Its immuno-suppressive activity may be disadvantageous for the therapy of cancers. A novel polymeric micelle system containing TP (TP-PM) was constructed by the solvent evaporation method using methoxypolyethylene glycol-poly(d,l-lactic acid)-block copolymer as the carrier, and was characterised using photon correlation spectroscopy, transmission electron microscopy and high performance liquid chromatography. The anti-tumour and immuno-modulation effects of TP-PM were evaluated in sarcoma 180-bearing mice and A2780 cells. Results demonstrated that TP-PM had an average diameter of 78.9 nm, encapsulation efficiency of 66.7%, core-shell morphology and a long-term stability. TP-PM could significantly inhibit tumour growth via intravenous injections at the dose levels of 0.0375, 0.075 and 0.15 mg/kg, and their inhibition rates were 42.5%, 46.0% and 49.9%, respectively; they showed similar cytotoxicity against A2780 cells compared to that of TP. Simultaneously, TP-PM had no effect on the thymus index, spleen index, spleen lymphocyte proliferation and the TNF-alpha and IL-2 levels in serum as compared with TP. Therefore, TP encapsulated in polymeric micelles does not demonstrate immuno-suppressive activity but does not lose its anti-tumour effect. These results show that polymeric micelles are a promising carrier for cancer therapy using TP.
雷公藤甲素（TP）具有抗肿瘤和免疫抑制活性。其免疫抑制活性可能对癌症治疗不利。以甲氧基聚乙二醇-聚（d，l-乳酸）-嵌段共聚物为载体，采用溶剂蒸发法构建了一种含TP的新型聚合物胶束系统（TP-PM），并通过光子相关光谱、透射电子显微镜和高效液相色谱对其进行了表征。在荷肉瘤180小鼠和A2780细胞中评估了TP-PM的抗肿瘤和免疫调节作用。结果表明，TP-PM的平均直径为78.9nm，包封率为66.7%，具有核壳形态和长期稳定性。TP-PM通过静脉注射在0.0375、0.075和0.15mg/kg剂量水平下可显著抑制肿瘤生长，其抑制率分别为42.5%、46.0%和49.9%；与TP相比，它们对A2780细胞表现出相似的细胞毒性。同时，与TP相比，TP-PM对胸腺指数、脾脏指数、脾脏淋巴细胞增殖以及血清中TNF-α和IL-2水平均无影响。因此，包裹在聚合物胶束中的TP不表现出免疫抑制活性，但不会丧失其抗肿瘤作用。这些结果表明，聚合物胶束是一种有前途的用于TP癌症治疗的载体。
