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  • Title: [Selective tumor-accumulation of HPMA copolymer-mitoxantrone conjugates].
    Author: Huang Y, Zhang ZR.
    Journal: Yao Xue Xue Bao; 2004 May; 39(5):374-9. PubMed ID: 15338883.
    Abstract:
    AIM: To increase the accumulation of mitoxantrone in solid tumor by synthesis and characterization of N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-mitoxantrone conjugate (p-DHAQ). METHODS: HPMA copolymer-mitoxantrone conjugate was prepared by free radical precipitation copolymerization method. The in vitro stability of conjugate was investigated under different conditions. Biodistribution was examined in mice bearing Ehrlich solid tumor. RESULTS: The p-DHAQ conjugate was characterized by UV, HPLC and size exclusion chromatography. The conjugate was stable in buffers of different pH and in mice plasma while the rate of drug liberation was faster in tumor. It appeared that the circulation lifetime of HPMA copolymer-bound mitoxantrone were three times more than that of the drug in free form. The AUC of p-DHAQ was three times more than the AUC of free drug. The p-DHAQ level in heart was five times lower than free drug. This reduces the possibility of toxicity to the heart. CONCLUSION: HPMA copolymer-mitoxantrone conjugate was successfully synthesized and characterized. The biodistribution results showed the possibility of targeting anticancer drug-mitoxantrone with secondary amino residue to the tumor tissue by HPMA copolymer as carrier.
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