Journal
ADVANCED ENGINEERING MATERIALS
Volume 12, Issue 9, Pages B496-B503Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adem.200980085
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Funding
- National Natural Science Foundation of China [50973071]
- Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry
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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.
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