Preparation, pharmacokinetics, biodistribution, antitumor efficacy and safety of Lx2-32c-containing liposome.
Preparation, pharmacokinetics, biodistribution, antitumor efficacy and safety of Lx2-32c-containing liposome.
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DOI：
10.1371/journal.pone.0114688
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Fu F
中科院分区：
文献类型：
--
作者：
Wang H;Zhang J;Lv G;Ma J;Ma P;Du G;Wang Z;Tian J;Fang W;Fu F
Lx 2 - 32 c是一种新的紫杉烷，已被证明对不同类型的肿瘤具有强大的抗肿瘤活性，包括几种紫杉醇耐药肿瘤。由于紫杉烷的递送载体（包括Cremophor EL）都与严重的毒性作用相关，因此已经开发了基于脂质体的Lx 2 - 32 c。在本研究中，基于脂质体的Lx 2 - 32 c的药代动力学，生物分布，抗肿瘤疗效和安全性特征进行了探索，并与基于Cremophor的Lx 2 - 32 c进行了比较。结果表明，脂质体Lx 2 - 32 c与Cremophor Lx 2 - 32 c具有相似的抗肿瘤作用，但骨髓毒性和心脏毒性明显低于Cremophor Lx 2 - 32 c，特别是关于低比例的超敏反应。在比较这两种递送方式时，使用Lx 2 - 32 c脂质体制剂的靶向是上级的;其在肿瘤中的摄取显著高于在骨髓和心脏中的摄取。因此，我们的数据表明，Lx 2 - 32 c脂质体是一种新型替代制剂，具有与基于克列莫佛的Lx 2 - 32 c相当的抗肿瘤疗效和上级安全性特征，这可能与改善的药代动力学和生物分布特征有关。总之，Lx 2 - 32 c脂质体可能是进一步开发的有前景的替代制剂。
Lx2-32c is a novel taxane that has been demonstrated to have robust antitumor activity against different types of tumors including several paclitaxel-resistant neoplasms. Since the delivery vehicles for taxane, which include cremophor EL, are all associated with severe toxic effects, liposome-based Lx2-32c has been developed. In the present study, the pharmacokinetics, biodistribution, antitumor efficacy and safety characteristics of liposome-based Lx2-32c were explored and compared with those of cremophor-based Lx2-32c. The results showed that liposome-based Lx2-32c displayed similar antitumor effects to cremophor-based Lx2-32c, but with significantly lower bone marrow toxicity and cardiotoxicity, especially with regard to the low ratio of hypersensitivity reaction. In comparing these two delivery modalities, targeting was superior using the Lx2-32c liposome formulation; it achieved significantly higher uptake in tumor than in bone marrow and heart. Our data thus suggested that the Lx2-32c liposome was a novel alternative formulation with comparable antitumor efficacy and a superior safety profiles to cremophor-based Lx2-32c, which might be related to the improved pharmacokinetic and biodistribution characteristics. In conclusion, the Lx2-32c liposome could be a promising alternative formulation for further development.
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影响因子：
3.4
作者：
Wang H;Cheng G;Du Y;Ye L;Chen W;Zhang L;Wang T;Tian J;Fu F
通讯作者：
Fu F
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：
11.5
作者：
Kim, TY;Kim, DW;Bang, YJ
通讯作者：
Bang, YJ
DOI：
10.1124/jpet.102.037119
发表时间：
2002-10-01
影响因子：
3.5
作者：
Phillips, WT;Medina, LA;Goins, B
通讯作者：
Goins, B
影响因子：
3.1
作者：
ROSA, P;CLEMENTI, F
通讯作者：
CLEMENTI, F