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Journal of Polymer Research

, Volume 14, Issue 3, pp 207–213 | Cite as

Application of 2-hydroxyethyl methacrylate polymers in controlled release of 5-aminosalicylic acid as a colon-specific drug

  • Mirzaagha Babazadeh
  • Ladan Edjlali
  • Lida Rashidian
Article

Abstract

Acrylic type polymeric systems having degradable ester bonds linked to 5-aminosalicylic acid were synthesized and evaluated as materials for drug delivery. 5-Aminosalicylic acid, as an important drug in the treatment of inflammatory bowel diseases, was linked to 2-hydroxyethyl methacrylate by activated ester methodology in two-step and one-pot procedures to obtain methacryloyloxyethyl 5-amino salicylate. The resulting methacrylic derivative of 5-aminosalicylic acid was copolymerized with methacrylamide, 2-hydroxyethyl methacrylate and methyl methacrylate (in 1:3 mole ratio) by free radical polymerization method in N,N-dimethylformamide solution, utilizing α,ά-azoisobutyronitrile as initiator at the temperature range of 65–70 °C. The obtained polymers were characterized by FT-IR, 1H NMR, 13C NMR and elemental analysis. The average molecular weights of the polymers bearing drug units as side substituents of the acrylic backbone were determined by gel permeation chromatography and their polydispersity indices resulted in the range of 1.6–1.8. Release studies of 5-aminosalicylic acid were performed into dialysis bags by hydrolysis in buffered solutions (pH 1, 7 and 8) at 37 °C. Detection of hydrolysis by UV spectroscopy at selected intervals showed that the drug can be released by selective hydrolysis of the ester bond at the side of drug moiety. The release profiles indicated that the hydrolytic behavior of polymeric prodrugs is strongly based on the polymer hydrophilicity and the pH value of the hydrolysis solution. The results suggest that these systems could be useful for preparation of a controlled release formulation of 5-aminosalicylic acid in colon.

Key words

5-aminosalicylic acid controlled release 2-hydroxyethyl methacrylate methacrylic polymers pH-sensitive polymers polymeric prodrugs 

References

  1. 1.
    Heller J (1996) In: Ratner BD, Hoffmann AS, Schoen FJ, Lemons JE (eds) An introduction to materials in medicine. Academic, London, p 346Google Scholar
  2. 2.
    Hoste K, De Winne K, Schacht E (2004) Int J Pharm 277:119CrossRefGoogle Scholar
  3. 3.
    Lewis DH (1990) In: Chasin M, Langer R (eds) Biodegradable polymers as drug delivery systems. Marcel Dekker, New York p 1Google Scholar
  4. 4.
    Babazadeh M (2006) Int J Pharm 316:68CrossRefGoogle Scholar
  5. 5.
    Zovko M, Zorc B, Novak P, Tepes P, Cetina-Cizmek B, Horvat M (2004) Int J Pharm 285:35Google Scholar
  6. 6.
    Davaran S, Hanaee J, Khosravi A (1999) J Control Realease 58:279CrossRefGoogle Scholar
  7. 7.
    Van den Mooter G, Offringa M, Kalala W, Samyn C, Kinger R (1995) Pharm Sci 5:36Google Scholar
  8. 8.
    Rihova B, Rathi C, Kopeckova P, Kopecek J (1992) Int J Pharm 87:105CrossRefGoogle Scholar
  9. 9.
    Van den Mooter G, Samyn C, Kinget R (1994) Pharm Res 11:1737CrossRefGoogle Scholar
  10. 10.
    McLeod AD, Friend DR, Tozer TN (1994) J Pharm Sci 83:1284CrossRefGoogle Scholar
  11. 11.
    Ardizzone S, Porro GB (1998) Drugs 55:519CrossRefGoogle Scholar
  12. 12.
    Cheng G, An F, Zou MJ, Sun J, Hao XH, He YX (2004) World J Gastroenterol 10:1769Google Scholar
  13. 13.
    Arshadi R (1993) Adv Polym J 111:1CrossRefGoogle Scholar
  14. 14.
    Akashi M, Tanaka Y, Miazaki T, Miyauchi N (1987) J Bioact Compat Polym 2:120CrossRefGoogle Scholar
  15. 15.
    Kuzuya M, Kondo S, Noguchi M (1991) Macromolecules 24:4047CrossRefGoogle Scholar
  16. 16.
    Chang CH, Sheu YM, Hu WP, Wang LF, Chen JS (1998) J Polym Sci Polym Chem 36:1481CrossRefGoogle Scholar
  17. 17.
    Safa KD, Babazadeh M (2004) Eur Polym J 40:1659CrossRefGoogle Scholar
  18. 18.
    Safa KD, Babazadeh M, Namazi H, Mahkam M, Asadi MG (2004) Eur Polym J 40:459CrossRefGoogle Scholar
  19. 19.
    Namazi H, Babazadeh M, Sarabi A, Entezami A (2001) J Polym Mater 18:301Google Scholar
  20. 20.
    Harris FW (1984) In: Langer RS, Wise DL (eds) Medical application of controlled release. CRC, Florida, p 103Google Scholar
  21. 21.
    Akashi M, Tanaka Y, Miazaki T, Miyauchi N (1987) J Bioact Compat Polym 2:120CrossRefGoogle Scholar
  22. 22.
    Kuzuya M, Kondo S (1991) Chem Pharm Bull 39:3018Google Scholar
  23. 23.
    Akashi M (1993) In: Tsuruta T (ed) Biomedical applications of polymeric materials. CRC, Florida, p 176Google Scholar

Copyright information

© Springer Science+Business Media, Inc. 2007

Authors and Affiliations

  • Mirzaagha Babazadeh
    • 1
  • Ladan Edjlali
    • 1
  • Lida Rashidian
    • 1
  1. 1.Laboratory of Organic Chemistry Research, Department of Applied ChemistryIslamic Azad University, Tabriz BranchTabrizIran

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