School of Pharmacy, Yantai University & State Key Laboratory of Long-acting and Targeting Drug Delivery Technologies, Yantai, Shandong 264003, PR China.
Food Chem Toxicol. 2013 Feb;52:200-6. doi: 10.1016/j.fct.2012.11.004. Epub 2012 Nov 10.
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.
紫杉醇经腹腔给药在治疗卵巢癌方面显示出了更好的疗效。然而，基于聚山梨醇酯的紫杉醇的剂量限制性毒性是严重的腹痛，可能是由赋形剂（聚山梨醇酯/乙醇）引起的。力扑素，一种紫杉醇脂质体，已在中国广泛应用于卵巢癌的静脉给药治疗。为了寻找腹腔内给予力扑素的潜在益处，我们假设力扑素可以调节紫杉醇的毒性，而不影响其抗肿瘤活性，与基于聚山梨醇酯的紫杉醇（PTX）相比。在 NuTu19 卵巢癌荷瘤大鼠中评估了抗肿瘤作用、骨髓毒性、心脏毒性和生物分布，以及正常小鼠的腹痛。力扑素与 PTX 具有相似的抗肿瘤作用，但骨髓毒性和心脏毒性明显较低。此外，与 PTX 相比，力扑素在血浆中的药物暴露相似，但在肿瘤和盆腔淋巴结中的暴露更高，在骨髓和心脏中的暴露更低。此外，力扑素引起的腹痛明显比 PTX 轻。这些数据表明，与 PTX 相比，力扑素通过腹腔途径给药具有相似的抗肿瘤作用和更好的淋巴靶向性，同时毒性降低，这可能与改变的生物分布有关。因此，力扑素可能是一种有吸引力的治疗卵巢癌的药物，值得进一步研究。
