In vitro release study, in vivo evaluation of biodistribution and antitumor activity of HPMA copolymer-5-fluorouracil conjugates.
- Author:
Fang YUAN
1
;
Zhi-Rong ZHANG
;
Yun-Xia YANG
;
Yuan HUANG
Author Information
1. West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
- Publication Type:Journal Article
- MeSH:
Acrylamides;
pharmacokinetics;
pharmacology;
Animals;
Antimetabolites, Antineoplastic;
pharmacokinetics;
pharmacology;
Area Under Curve;
Cell Line, Tumor;
Drug Carriers;
Drug Compounding;
Female;
Fluorouracil;
pharmacokinetics;
pharmacology;
Liver Neoplasms, Experimental;
metabolism;
pathology;
Mice;
Neoplasm Transplantation;
Random Allocation;
Tissue Distribution;
Tumor Burden;
drug effects
- From:
Acta Pharmaceutica Sinica
2008;43(11):1152-1156
- CountryChina
- Language:Chinese
-
Abstract:
The in vitro release behavior, in vivo biodistribution and antitumor activity of N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-5-fluorouracil conjugates (P-FU) were studied. The in vitro release behavior was evaluated by determining the amount of 5-fluorouracil (5-FU) released from P-FU in mice plasma at 37 degrees C. The in vivo biodistribution and therapeutic evaluation were investigated with Kunming mice bearing hepatoma 22 (H22). The in vitro half-life (t1/2) of P-FU in mice plasma was 32.4 h. It appeared that the circulation life time of the conjugates were 166 times longer than that of 5-FU. The AUC and t1/2 of P-FU in tumor were 3.3 times and 2.3 times more than those of 5-FU, respectively. Therapeutic evaluation also demonstrated that the treatment with P-FU displayed stronger inhibition of the tumor growth when compared with that of 5-FU (P < 0.05). HPMA copolymer is a potential carrier for 5-FU for effective treatment of cancer.
