Hypersensitivity reaction studies of a polyethoxylated castor oil-free, liposome-based alternative paclitaxel formulation.
Hypersensitivity reaction studies of a polyethoxylated castor oil-free, liposome-based alternative paclitaxel formulation.
复制标题
DOI：
10.3892/mmr.2013.1264
复制
发表时间：
2013-03
影响因子：
3.4
通讯作者：
Fu F
中科院分区：
文献类型：
--
作者：
Wang H;Cheng G;Du Y;Ye L;Chen W;Zhang L;Wang T;Tian J;Fu F
商业药物紫杉醇（Taxol）可能会引起与聚乙氧基化蓖麻油-乙醇溶剂相关的过敏反应。为了克服这些问题，我们开发了一种基于脂质体的聚乙氧基化无蓖麻油替代紫杉醇制剂，称为力扑素。在这项研究中，我们进行了体外和体内实验来比较力扑素和紫杉醇的安全性，特别是超敏反应。首先，使用瑞士小鼠确定致死剂量，然后评估超敏反应，随后进行血清 SC5b-9 和肺组织胺的组织病理学检查和酶联免疫吸附测定（ELISA）。此外，还使用健康人血清来分析体外补体激活。最后采用MTT法测定体外抗增殖活性。我们的数据清楚地表明，力扑素表现出更高的安全性，并且不会诱发超敏反应或与超敏反应相关的肺部病变，这可能与力扑素在体内不会激活补体或增加组胺释放有关。此外，力扑素在体外不会促进健康人血清中的补体激活，并且表现出与紫杉醇类似的抗人癌细胞增殖活性。因此，改进的紫杉醇配方表现出更好的安全性和与紫杉醇相当的细胞毒活性，可能会给癌症患者带来许多好处。
The commercial drug paclitaxel (Taxol) may introduce hypersensitivity reactions associated with the polyethoxylated castor oil-ethanol solvent. To overcome these problems, we developed a polyethoxylated castor oil-free, liposome-based alternative paclitaxel formulation, known as Lipusu. In this study, we performed in vitro and in vivo experiments to compare the safety profiles of Lipusu and Taxol, with special regard to hypersensitivity reactions. First, Swiss mice were used to determine the lethal dosages, and then to evaluate hypersensitivity reactions, followed by histopathological examination and enzyme-linked immunosorbent assays (ELISAs) of serum SC5b-9 and lung histamine. Additionally, healthy human serum was used to analyze in vitro complement activation. Finally, an MTT assay was used to determine the in vitro anti-proliferation activity. Our data clearly showed that Lipusu displayed a much higher safety margin and did not induce hypersensitivity or hypersensitivity-related lung lesions, which may be associated with the fact that Lipusu did not activate complement or increase histamine release in vivo. Moreover, Lipusu did not promote complement activation in healthy human serum in vitro, and demonstrated anti-proliferative activity against human cancer cells, similar to that of Taxol. Therefore, the improved formulation of paclitaxel, which exhibited a much better safety profile and comparable cytotoxic activity to Taxol, may bring a number of benefits to cancer patients.
登录
查看更多内容
新型紫杉烷Lx2-32c及其体内外抗肿瘤活性
影响因子：
9.7
作者：
Wang, Hongbo;Li, Hongyan;Chen, Xiaoguang
通讯作者：
Chen, Xiaoguang
影响因子：
4.4
作者：
Bossi, F;Fischetti, F;Tedesco, F
通讯作者：
Tedesco, F
DOI：
10.1016/j.ejpb.2004.06.009
发表时间：
2005-01-01
影响因子：
4.9
作者：
Zhang, JA;Anyarambhatla, G;Ahmad, I
通讯作者：
Ahmad, I
影响因子：
1.7
作者：
Xia, Xue-Jun;Guo, Rui-Fang;Wang, Ren-Yun
通讯作者：
Wang, Ren-Yun
DOI：
10.1080/15287397709529614
发表时间：
1977-01-01
期刊：
JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH
影响因子：
--
作者：
ROSIELLO, AP;ESSIGMANN, JM;WOGAN, GN
通讯作者：
WOGAN, GN