title: Antitumor effect and toxicity of Lipusu in rat ovarian cancer xenografts.
abstract: 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 abdominalpain 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 abdominalpain 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.
authors.affiliation: School of Pharmacy, Yantai University & State Key Laboratory of Long-acting and Targeting Drug Delivery Technologies, Yantai, Shandong 264003, PR China. yeliang@luye.cn
authors.forename: Liang
authors.initials: L
authors.lastname: Ye
authors.forename: Jie
authors.initials: J
authors.lastname: He
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Hu
authors.forename: Qiuju
authors.initials: Q
authors.lastname: Dong
authors.forename: Hongbo
authors.initials: H
authors.lastname: Wang
authors.forename: Fenghua
authors.initials: F
authors.lastname: Fu
authors.forename: Jingwei
authors.initials: J
authors.lastname: Tian
mesh_terms: D015746:Abdominal Pain / Q000139:chemically induced; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D001853:Bone Marrow / Q000187:drug effects; D016503:Drug Delivery Systems; D005260:Female; D006321:Heart / Q000187:drug effects; D007274:Injections, Intraperitoneal; D008081:Liposomes / Q000008:administration & dosage* / Q000633:toxicity; D051379:Mice; D009206:Myocardium / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage* / Q000494:pharmacology / Q000633:toxicity; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008081:Liposomes; C022131:cremophor; D011092:Polyethylene Glycols; D017239:Paclitaxel