In Vivo Evaluation of a pH‐Sensitive Pullulan–Doxorubicin Conjugate
In Vivo Evaluation of a pH‐Sensitive Pullulan–Doxorubicin Conjugate
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DOI：
10.1002/adem.200980085
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发表时间：
2010-09
影响因子：
3.6
通讯作者：
D. Lu;Jie Liang;Yujiang Fan;Z. Gu;Xingdong Zhang
中科院分区：
文献类型：
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作者：
D. Lu;Jie Liang;Yujiang Fan;Z. Gu;Xingdong Zhang
通过与阿霉素的溶血活性、生物分布、生物安全性、心脏毒性和抗肿瘤作用的比较，对pH敏感的普鲁兰-阿霉素结合物进行了体内评价。溶血实验表明，阿霉素在2 5 0 mg L−1溶液中的溶血率为8.38%，而普鲁兰-阿霉素结合物在相同药物浓度下无溶血作用。普鲁兰-阿霉素结合物的循环时间比阿霉素长，经侧静脉给药后240分钟内，普鲁兰-阿霉素结合物在肿瘤组织中的浓度约为阿霉素的两倍。体内安全性研究表明，普鲁兰-阿霉素结合物比游离阿霉素具有更好的生物安全性，经急性毒性、全身毒性和组织病理学观察证实。经透射电子显微镜和心电图证实，普鲁兰-阿霉素结合物的心脏毒性远低于游离阿霉素。体内抗肿瘤活性实验表明，普鲁兰-阿霉素结合物具有与阿霉素相当的抗肿瘤效果。
A pH‐sensitive pullulan–doxorubicin conjugate is evaluated in vivo by comparison with doxorubicin with respect to hemolytic activity, biodistribution, biosafety, cardiotoxicity and antitumor effects. Hemolytic studies show that doxorubicin caused 8.38% hemolysis at 250 mg L−1, while no hemolysis is observed with pullulan–doxorubicin conjugate at the same drug concentration. The circulation time of pullulan–doxorubicin conjugate is relatively longer than that of doxorubicin, and the concentration in tumors for pullulan–doxorubicin conjugate increases to about double that of doxorubicin within 240 min after injection of drugs via the lateral vein. In vivo safety research shows that pullulan–doxorubicin conjugate shows better biosafety than free doxorubicin, confirmed by acute toxicity, systemic toxicity and histopathological observations. The cardiotoxicity of pullulan–doxorubicin conjugate is much lower than that of free doxorubicin, as confirmed by TEM and ECG. In vivo antitumor activity assays show that the pullulan–doxorubicin conjugate has an antitumor efficacy comparable to that of doxorubicin.