Acute Toxicity Study of Cisplatin Loaded Long-Circulating and pH-Sensitive Liposomes Administered in Mice

Acute Toxicity Study of Cisplatin Loaded Long-Circulating and pH-Sensitive Liposomes Administered in Mice
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DOI:
10.1166/jbn.2012.1388
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发表时间:
2012-04-01
影响因子:
2.9
通讯作者:
De Oliveira, Monica C.
De Oliveira, Monica C.
中科院分区:
工程技术3区
文献类型:
--
作者:
Leite, Elaine A.;Lana, Angela M. Q.;De Oliveira, Monica C.

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顺铂(CDDP)是一种活性很高的细胞毒性药物,但会引起严重的副作用,即肾毒性,这限制了治疗。本研究的目的是评价含顺铂的长循环和pH敏感性脂质体(SpHL-CDDP)与游离CDDP静脉给药后的急性毒性。分别给予不同剂量的游离CDDP或SpHL-CDDP后,记录体重,计算LD 50和最大耐受剂量(MTD)。采集血样进行血液学和生化分析。取出肾脏、肝脏、脾脏和骨髓进行组织病理学检查。在用游离CDDP和SpHL-CDDP以100 mg/kg的剂量处理后,在雄性和雌性小鼠中可以观察到小于15%的体重减轻。
Cisplatin (CDDP) is a very active and cytotoxic agent but causes severe side effects, namely nephrotoxicity, which limits the therapy. The present study aimed to evaluate the acute toxicity of long-circulating and pH-sensitive liposomes containing cisplatin (SpHL-CDDP), as compared to free CDDP, after their intravenous administration in mice. After the administration of free CDDP or SpHL-CDDP at different doses, the body weight was recorded and the LD50 and the maximum tolerated dose (MTD) were calculated. Blood samples were collected for hematological and biochemical analysis. Kidneys, liver, spleen, and bone marrow were removed for histopathological examination. A reduction of body weight of less than 15% could be observed in male and female mice after treatment with free CDDP and SpHL-CDDP at doses of