In Vivo Evaluation of a pH‐Sensitive Pullulan–Doxorubicin Conjugate

Abstract 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.