Journal
FOOD AND CHEMICAL TOXICOLOGY
Volume 52, Issue -, Pages 200-206Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fct.2012.11.004
Keywords
Lipusu; Liposome; Ovarian cancer; Intraperitoneal administration; Antitumor; Toxicity
Categories
Funding
- National Natural Science Foundation of China [81001661]
- Shandong Province Young and Middle-Aged Scientists Research Awards Fund [BS2009SW012]
- Taishan Scholar Project
- Technology Development Program Projects of Shandong Province [2011YD18075]
- National Basic Research Program of China [2012CB724003]
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Paclitaxel has yielded superior therapeutic effects in treating ovarian cancer after intraperitoneal (i.p.) injection. However, the dose-limiting toxicity of Cremophor-based paclitaxel was severe abdominal pain, likely caused by the excipients (Cremophor/ethanol). Lipusu, a paclitaxel liposome, has been widely applied for the treatment of ovarian cancer by intravenous administration in China. In order to find potential benefits of i.p. administration of Lipusu, we suppose that Lipusu could modulate paclitaxel toxicity without affecting antitumor activity compared with Cremophor-based paclitaxel (PTX). Antitumor effects, bone marrow toxicity, cardiotoxicity and biodistributions in NuTu19 ovarian cancer-bearing rats, as well as the abdominal pain in normal mice were evaluated. Lipusu exerted similar antitumor effects similar to PTX, but much lower bone marrow toxicity and cardiotoxicity. Furthermore, Lipusu exhibited similar plasma drug exposure, higher exposure in tumor and pelvic lymph nodes and lower exposure in bone marrow and heart compared with PTX. Additionally, Lipusu induced notably lighter abdominal pain than PTX. These data suggested that Lipusu has similar antitumor effect and superior lymphatic targeting with reduced toxicities compared with PTX via i.p. route, which could be related with altered biodistributions. Therefore, Lipusu could be attractive for further evaluation of treating ovarian cancer by i.p. administration in clinic. (C) 2012 Elsevier Ltd. All rights reserved.
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