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Tissue distribution and pharmacodynamics of chitosan-coated mitoxantrone liposomes in the tumor-bearing mice[J]. Journal of China Pharmaceutical University, 2010, 41(4): 353-359.
Citation: Tissue distribution and pharmacodynamics of chitosan-coated mitoxantrone liposomes in the tumor-bearing mice[J]. Journal of China Pharmaceutical University, 2010, 41(4): 353-359.

Tissue distribution and pharmacodynamics of chitosan-coated mitoxantrone liposomes in the tumor-bearing mice

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  • In vitro release,tissue distribution and pharmacodynamics of chitosan-coated mitoxantrone (MTO) liposomes (CL-MTO) in tumor-bearing mice were investigated.In vitro releases of CL-MTO and mitoxantrone liposomes (L-MTO) were determined by dialysis.After intravenous injection of I-MTO (mitoxantrone saline solution),L-MTO and CL-MTO to tumor-bearing mice,levels of MTO in the biological samples were assayed by HPLC,and the tissue distribution and targeting performance of the three different formulations were evaluated,and their pharmacodynamics were determined by their antitumor efficacy. It was found that the cumulative release of CL-MTO and L-MTO in various dissolution media (pH 6.0-7.4) were around 30.81%-16.15% and 41.84%-32.51%,respectively.Chitosan-coating retarded in vitro release of MTO from the liposomes.If compared to I-MTO,the study of tissue distribution of CL-MTO and L-MTO proved that the area under the plasma concentration-time curve (AUCplasma) increased significantly,while the area under the heart and kidney tissue level-time curve (AUCheart and AUCkidney) decreased.The ratio of the AUC of plasma to that AUC of reticulo-endothelial system (Blood/RES) of CL-MTO was 1.70-fold higher than that of L-MTO.Moreover,there existed higher relative tumor exposure (1.74-fold) and higher therapeutic efficacy of CL-MTO than L-MTO.This study indicated that chitosan-coating increased in vitro/in vivo stability of liposomes and their tumor-targeting potentials,as well as improved the therapeutic efficacy of liposomes.
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