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.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Nichifora M, Schachta EH, Seymour LW (1997) Polymeric prodrugs of 5-fluorouracil. J Control Release 48:165–178
Akashi M, Takemoto K (1990) New aspects of polymer drugs. Adv Polymer Sci 97:108–146
Ouchi T, Fujino A, Tanaka K et al (1990) Synthesis and antitumor activity of conjugates of poly(α-malic acid) and 5-fluorouracil bound via ester, amide or carbamoyl bonds. J Control Release 12:143–153
Ouchi T, Hagihara Y, Takahashi K et al (1992) Synthesis and anti-tumor activity of poly(ethylene glycol)s linked to 5-fluorouracil via urethane or urea bonds. Drug Design Disc 9:93–105
Ouchi T, Banba T, Matsumoto T et al (1990) Synthesis and anti-tumor activity of conjugates of 5-fluorouracil and chito-oligosaccharides involving a hexamethylene spacer group and carbamoyl bonds. Drug Design Del 6:281–287
Bundgaard H (1989) The double prodrug concept and its application. Adv Drug Del Rev 3:39–65
Amsberry KL, Borchardt RT (1991) Amine prodrugs which utilise hydroxy amide lactonization. I. a potential redox-sensitive amide prodrug. Pharm Res 8:323–330
Vinsovam J, Vavrikova E (2008) Recent advances in drugs and prodrugs design of chitosan. Curr Pharm Design 14:1311–1326
Liang Y, Liu W, Han B et al (2011) Fabrication and characters of a corneal endothelial cells scaffold based on chitosan. J Mater Sci Mater Med 22:175–183
Liang Y, Liu W, Han B et al (2011) An in situ formed biodegradable hydrogel for reconstruction of the corneal endothelium. Colloid Surface B 82:1–7
Li M, Han B, Liu W (2011) Preparation and properties of a drug release membrane of mitomycin C with N-succinyl-hydroxyethyl chitosan. J Mater Sci Mater Med 22:2745–2755
Udo K, Hokonohara K, Motoyama K et al (2010) 5-Fluorouracil acetic acid/beta-cyclodextrin conjugates: drug release behavior in enzymatic and rat cecal media. Int J Pharm 388:95–100
Wang Q, Liu X, Liu L et al (2007) Synthesis and evaluation of the 5-fluorouracil- pectin conjugate targeted at the colon. Med Chem Res 16:370–379
Luo Q, Wang P, Miao Y et al (2012) A novel 5-fluorouracil prodrug using hydroxyethylstarch as a macromolecular carrier for sustained release. Carbohydr Polym 87:2642–2647
Zhang Z, Zhang Q, Wang J (2010) Synthesis and drug release in vitro of porphyran carrying 5-fluorouracil. Carbohydr Polym 79:628–632
Peppas L (1997) Polymers in controlled drug delivery. Med Plast Biomater 4:34–44
Prabaharan M, Reis R, Mano J (2007) Carboxymethyl chitosan-graft-phosphatidylethanolamine: amphiphilic matrices for controlled drug delivery. React & Funct Polym 67:43–52
Yang Z, Wang L, Yang X et al (2000) Pharmacological study on antitumor activity of 5- fluorouracil 1-acetic acid and its rare earth complexes. J Rare Earth 18:140–143
Acknowledgments
This work was financially supported by the National Natural Sciences Foundation of China (No.30800193). Dr. Joensuu Päivi from Univeristy of Oulu is appreciated for the expert help with mass spectrometry.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Peng, Y., Liu, W., Han, B., Zhou, R. (2014). Synthesis and Controlled Release of 5-Fluorouracil from Hydroxyethylchitosan: Based Polymer Prodrug. In: Zhang, TC., Ouyang, P., Kaplan, S., Skarnes, B. (eds) Proceedings of the 2012 International Conference on Applied Biotechnology (ICAB 2012). Lecture Notes in Electrical Engineering, vol 250. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-37922-2_77
Download citation
DOI: https://doi.org/10.1007/978-3-642-37922-2_77
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-37921-5
Online ISBN: 978-3-642-37922-2
eBook Packages: EngineeringEngineering (R0)