Department of Pharmaceutics, National Institute of Pharmaceutical Education & Research, S.A.S. Nagar, Mohali 160062, Punjab, India.
Pharm Res. 2012 Sep;29(9):2522-33. doi: 10.1007/s11095-012-0783-8. Epub 2012 Jun 6.
To evaluate in vivo doxorubicin-loaded (PEG)(3)-PLA nanopolymersomes (PolyDoxSome) using 7,12-dimethyl benz[α]anthracene (DMBA)-induced mammary carcinoma rat model compared to marketed formulation LipoDox™.
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 hμg/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™, it differs in size (171 vs. <100 nm), plasma circulation half life (22 vs. 35 h), C(max) (34 vs. 67 μg/mL), and AUC (568 vs. 2291 hμg/mL), however PolyDoxSome was comparable on efficacy and toxicity profile of LipoDox™.
Results suggest that PolyDoxSome has better in vivo profile than free doxorubicin and comparable efficacy and toxicity to LipoDox™.
与市售制剂 LipoDox™相比，在 7,12-二甲基苯并[a]蒽（DMBA）诱导的乳腺癌大鼠模型中评估载多柔比星（PEG）（3）-PLA 纳米聚合物囊泡（PolyDoxSome）的体内情况。
使用平均肿瘤体积约为 2 cm3 的 Sprague Dawley 雌性大鼠进行药代动力学、生物分布、抗肿瘤疗效和毒性研究。
该研究表明，与游离多柔比星相比，PolyDoxSome 具有更高的 AUC（569 比 4 hμg/mL）、更长的血浆循环半衰期（21.9 比 0.49 h）、更低的清除率（10.5 比 1579 mL/h/kg）和分布容积（137.7 比 1091 mL/kg）。组织分布谱显示，与游离多柔比星相比，肿瘤中多柔比星浓度增加，心脏中多柔比星浓度降低。肝肾功能试验、心肌酶谱、血液学检查和体重毒性研究表明，PolyDoxSome 的耐受性优于游离多柔比星。当 PolyDoxSome 与 LipoDox™ 进行比较时，其在粒径（171 比 <100nm）、血浆循环半衰期（22 比 35 h）、Cmax（34 比 67μg/mL）和 AUC（568 比 2291 hμg/mL）方面存在差异，然而 PolyDoxSome 在疗效和毒性方面与 LipoDox™ 相当。
结果表明，PolyDoxSome 具有比游离多柔比星更好的体内特性，并且在疗效和毒性方面与 LipoDox™ 相当。
