In Vivo Evaluation of Doxorubicin-Loaded (PEG)3-PLA Nanopolymersomes (PolyDoxSome) Using DMBA-Induced Mammary Carcinoma Rat Model and Comparison with Marketed LipoDox™
In Vivo Evaluation of Doxorubicin-Loaded (PEG)3-PLA Nanopolymersomes (PolyDoxSome) Using DMBA-Induced Mammary Carcinoma Rat Model and Comparison with Marketed LipoDox™
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DOI：
10.1007/s11095-012-0783-8
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发表时间：
2012-09-01
影响因子：
3.7
通讯作者：
Kumar, Neeraj
中科院分区：
文献类型：
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作者：
Ayen, Wubeante Yenet;Kumar, Neeraj
与市售制剂 LipoDox (TM) 相比，使用 7,12-二甲基苯并蒽 (DMBA) 诱导的乳腺癌大鼠模型评估体内阿霉素负载 (PEG)(3)-PLA 纳米聚合物囊泡 (PolyDoxSome) 与市售制剂 LipoDox (TM) 的比较。使用平均肿瘤体积约 2 cm(3) 的 Sprague Dawley 雌性大鼠进行药代动力学、生物分布、抗肿瘤功效和毒性研究。表明与游离阿霉素相比，PolyDoxSome 具有更高的 AUC（569 vs. 4 h*mu g/mL）、更长的血浆循环半衰期（21.9 vs. 0.49 h）、降低的清除率（10.5 vs. 1579 mL/h/kg）和分布容积（137.7 vs. 1091 mL/kg）。组织分布图显示与游离阿霉素相比，肿瘤中的阿霉素浓度增加，而心脏中的浓度降低。通过肝功能测试、心肌酶测定、血液学测试和体重进行的毒性研究表明，它比游离阿霉素具有更好的耐受性。当 PolyDoxSome 与 LipoDox (TM) 进行比较时，其大小（171 vs. < 100 nm）、血浆循环半衰期（22 vs. 35 h）、C-max（34 vs. 67 mu g/mL）和 AUC（568 vs. 2291 h*mu g/mL）有所不同，但 PolyDoxSome 在功效和毒性方面与 LipoDox (TM) 相当。结果表明PolyDoxSome 具有比游离阿霉素更好的体内特性，并且与 LipoDox (TM) 具有相当的功效和毒性。
To evaluate in vivo doxorubicin-loaded (PEG)(3)-PLA nanopolymersomes (PolyDoxSome) using 7,12-dimethyl benz[alpha]anthracene (DMBA)-induced mammary carcinoma rat model compared to marketed formulation LipoDox (TM).Sprague Dawley female rats with mean tumor volume of about 2 cm(3) were used for pharmacokinetics, biodistribution, antitumor efficacy and toxicity studies.This study demonstrates that PolyDoxSome has higher AUC (569 vs. 4 h*mu g/mL), longer plasma circulation half life (21.9 vs. 0.49 h), decreased clearance (10.5 vs. 1579 mL/h/kg) and volume of distribution (137.7 vs. 1091 mL/kg) as compared to free doxorubicin. Tissue distribution profile showed increased doxorubicin concentration in tumor and decreased concentration in heart as compared to free doxorubicin. The toxicity studies as measured from liver function tests, cardiac enzyme assays, hematology test and body weight has demonstrated that it is better tolerated than free doxorubicin. When PolyDoxSome was compared with LipoDox (TM), it differs in size (171 vs. < 100 nm), plasma circulation half life (22 vs. 35 h), C-max (34 vs. 67 mu g/mL), and AUC (568 vs. 2291 h*mu g/mL), however PolyDoxSome was comparable on efficacy and toxicity profile of LipoDox (TM).Results suggest that PolyDoxSome has better in vivo profile than free doxorubicin and comparable efficacy and toxicity to LipoDox (TM).