Biodistribution of N-(2-hydroxypropyl) methacrylamide copolymer-bound mitoxantrone in mice bearing Ehrlich solid tumor.
- Author:
Yuan HUANG
1
;
Zhirong ZHANG
;
Wensheng LIU
Author Information
1. West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
- Publication Type:Journal Article
- MeSH:
Acrylamides;
administration & dosage;
chemical synthesis;
pharmacokinetics;
Animals;
Antineoplastic Agents;
administration & dosage;
chemical synthesis;
pharmacokinetics;
Carcinoma, Ehrlich Tumor;
metabolism;
Drug Carriers;
administration & dosage;
chemical synthesis;
pharmacokinetics;
Drug Delivery Systems;
Mice;
Mitoxantrone;
administration & dosage;
chemical synthesis;
pharmacokinetics;
Polymers;
administration & dosage;
chemical synthesis;
pharmacokinetics;
Tissue Distribution
- From:
Journal of Biomedical Engineering
2004;21(6):930-934
- CountryChina
- Language:Chinese
-
Abstract:
N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-Mitoxantrone conjugates was successfully synthesized and characterized as an anti-cancer drug for solid tumors. The biodistribution and pharmacokinetics of the conjugates were examined in mice bearing Ehrlich solid tumor. The biodistribution of the HPMA copolymer-bound Mitoxantrone in tumor-bearing mice was significantly different from that of the free drug. It appeared that the circulation life times of the conjugates were three times more than those of the drugs in the free form. The concentrations of HPMA copolymer-bound Mitoxantrone in tumor reached maximum levels 24 h post injection. AUC is three times higher than that of free drug. The P-Mitoxantrone level in heart was five times lower than that of free drug. This reduces the possibility of toxicity to heart. In particular, HPMA copolymer-bound Mitoxantrone accumulated at higher levels in tumor tissues. This may be explained by "Enhanced Permeability and Retention effect" (EPR effect). These results show the possibility of targeting anticancer drug-Mitoxantrone with secondary amino residue to the tumor tissue by HPMA copolymer as carrier.
