[In vitro release study, in vivo evaluation of biodistribution and antitumor activity of HPMA copolymer-5-fluorouracil conjugates].
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.
Yuan
Fang
F
West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
Zhang
Zhi-Rong
ZR
Yang
Yun-Xia
YX
Huang
Yuan
Y
D000178:Acrylamides / Q000493:pharmacokinetics* / Q000494:pharmacology; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics* / Q000494:pharmacology; D019540:Area Under Curve; D045744:Cell Line, Tumor; D004337:Drug Carriers; D004339:Drug Compounding; D005260:Female; D005472:Fluorouracil / Q000493:pharmacokinetics* / Q000494:pharmacology; D008114:Liver Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D009368:Neoplasm Transplantation; D011897:Random Allocation; D014018:Tissue Distribution; D047368:Tumor Burden / Q000187:drug effects
D000178:Acrylamides; D000964:Antimetabolites, Antineoplastic; D004337:Drug Carriers; C032976:N-(2-hydroxypropyl)methacrylamide; D005472:Fluorouracil