Synthesis and Controlled Release of 5-Fluorouracil from Hydroxyethylchitosan: Based Polymer Prodrug
A novel water-soluble hydroxyethylchitosan-based polymer prodrug of 5-fluorouracil ((HECS-5-Fu) was synthesized through acetyl spacer via ester bond. The conjugated content of 5-Fu was 12.2 % (w). In phosphate buffer solution (pH 7.4) at 37 °C, HECS-5-Fu
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Synthesis and Controlled Release of 5-Fluorouracil from Hydroxyethylchitosan: Based Polymer Prodrug Yanfei Peng, Wanshun Liu, Baoqin Han and Ruixue Zhou Abstract A novel water-soluble hydroxyethylchitosan-based polymer prodrug of 5-fluorouracil ((HECS-5-Fu) was synthesized through acetyl spacer via ester bond. The conjugated content of 5-Fu was 12.2 % (w). In phosphate buffer solution (pH 7.4) at 37 °C, HECS-5-Fu slowly hydrolyzed to release 5-fluorouracil-1-yl acetic acid as characterized by RP-HPLC and LC–MS. The controlled release of drug from HECS-5-Fu powder sustained for more than 25 days. The in vitro experiment indicated that 5-fluorouracil-1-yl-acetic acid at concentration of 400 ug/mL inhibited the proliferation of about 40.0 % mouse fibroblast cell line L929. HECS-5-Fu could have a potential application as an antimetabolic material in glaucoma filtration device implantation.
Keywords Hydroxyethyl chitosan 5-Fluorouracil Prodrug Release Fibroblast
77.1 Introduction 5-fluorouracil (5-Fu), as an antimetabolite has shown significant antitumor activities. However, its short plasma circulation half-life, serious systemic toxicities, and poor tumor-targeting make it important to screen out more clinically efficient derivatives of 5-Fu, alternatively to prepare controlled and site-specific drug release system. Polymer materials like peptides, polysaccharides, and other natural products have recently attracted much attention as biodegradable drug carriers. A variety of macromolecular prodrugs of 5-Fu have been developed [1]. In most cases, the bioactivities are due to the free 5-Fu released by a nonspecific chemical hydrolysis Y. Peng (&) W. Liu B. Han R. Zhou College of Marine Life Sciences, Ocean University of China, Qingdao 266003, China e-mail: [email protected]
T.-C. Zhang et al. (eds.), Proceedings of the 2012 International Conference on Applied Biotechnology (ICAB 2012), Lecture Notes in Electrical Engineering 250, DOI: 10.1007/978-3-642-37922-2_77, Ó Springer-Verlag Berlin Heidelberg 2014
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of the ester, carbomate, amide bonds between the drug and the polymer backbone [2–5]. 5-Fu-polymer conjugates have also been reported to be able to provide sitespecific release of 5-Fu by a step-wise enzymatic and chemical cleavage of chemical bonds under the environmental conditions of target cells [6, 7]. Chitosan and its water-soluble derivatives have been extensively used in developing drug release systems in view of their good biocompatibility, biodegradability, nontoxicity, antibacterial, antitumor, and other bioactivities. Many reports are available on preparation of chitosan-based drug capsules, microspheres, nanoparticles, beads, gels, and films. Chitosan prodrug, in which drug is covalently linked onto chitosan chain has been found to be bioactive in the field of antibacteria, anticancer, and antioxidant [8]. Our previous studies show that a blend membrane based on hydroxyethylchitosan (HECS) has good biodegradability and histocompatibility, and can potential
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