Get access

Improved stability and tumor targeting of 5-fluorouracil by conjugation with hyaluronan

Authors

  • Zhikui Dong,

    1. Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu 610041, People's Republic of China
    Search for more papers by this author
  • Wenyi Zheng,

    1. Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu 610041, People's Republic of China
    Search for more papers by this author
  • Zaiyang Xu,

    1. Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu 610041, People's Republic of China
    Search for more papers by this author
  • Zongning Yin

    Corresponding author
    1. Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu 610041, People's Republic of China
    • Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu 610041, People's Republic of China. E-mail: yzn@scu.edu.cn

    Search for more papers by this author

Abstract

To circumvent the rapid clearance in vivo and consequent low tumor targeting of 5-fluorouracil (5-Fu), hyaluronan-5-fluorouracil conjugate (HA-5-Fu) was firstly synthesized and characterized. The stability of HA-5-Fu in vitro was evaluated by incubation with phosphate buffered saline, hyaluronidase solution, and mice plasma, respectively. The tumor targeting was tested by in vitro cytotoxicity evaluation and in vivo pharmacokinetics study in plasma and tumor. HA-5-Fu with drug loading of 87.674 mg/g was successfully obtained and confirmed. HA-5-Fu showed high stability in acidic environment and moderate stability under enzymatic cleavage. The enhanced cytotoxicity of HA-5-Fu over 5-Fu depended on drug concentration, incubation time, and cell lines type. The t1/2 of HA-5-Fu in plasma after injection of prodrug was extended up to 10 times compared with that of 5-Fu. Notably, AUC0–t in tumors of HA-5-Fu was 3.6 times higher than 5-Fu, demonstrating its excellent tumor targeting and quite promising prospect in anti-cancer therapy. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 927-932, 2013

Get access to the full text of this article

Ancillary