Improved stability and tumor targeting of 5‐fluorouracil by conjugation with hyaluronan. Issue 2 (11th April 2013)

• Record Type: Journal Article
• Authors: Dong, Zhikui; Zheng, Wenyi; Xu, Zaiyang; Yin, Zongning
• Is Part Of: Journal of applied polymer science. Volume 130:Issue 2(2013:Oct. 15)
• Page Start: 927
• Page End: 932
• Publication Date: 2013-04-11
• Subjects: Polymers -- Periodicals; Polymerization -- Periodicals; 668.9
• DOI: 10.1002/app.39247
• Languages: English
• ISSNs: 0021-8995

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>To circumvent the rapid clearance <italic>in vivo</italic> 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 <italic>in vitro</italic> was evaluated by incubation with phosphate buffered saline, hyaluronidase solution, and mice plasma, respectively. The tumor targeting was tested by <italic>in vitro</italic> cytotoxicity evaluation and <italic>in vivo</italic> 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 <italic>t</italic>_1/2 of HA‐5‐Fu in plasma after injection of prodrug was extended up to 10 times compared with that of 5‐Fu. Notably, AUC_{0–<italic>t</italic>} 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</p> </abstract>