Applied Biochemistry and Biotechnology

, Volume 164, Issue 2, pp 133–147 | Cite as

The Syntheses and Characterization of Molecularly Imprinted Polymers for the Controlled Release of Bromhexine

  • Saman Azodi-Deilami
  • Majid Abdouss
  • Mehran Javanbakht
Article

Abstract

Imprinted polymers are now being increasingly considered for active biomedical uses such as drug delivery. In this work, the use of molecularly imprinted polymers (MIPs) in designing new drug delivery devices was studied. Imprinted polymers were prepared from methacrylic acid (functional monomer), ethylene glycol dimethacrylate (cross-linker), and bromhexine (as a drug template) using bulk polymerization method. The influence of the template/functional monomer proportion and pH on the achievement of MIPs with pore cavities with a high enough affinity for the drug was investigated. The polymeric devices were further characterized by FT-IR, thermogravimetric analysis, scanning electron microscopy, and binding experiments. The imprinted polymers showed a higher affinity for bromhexine and a slower release rate than the non-imprinted polymers. The controlled release of bromhexine from the prepared imprinted polymers was investigated through in vitro dissolution tests by measuring absorbance at λ max of 310 nm by HPLC-UV. The dissolution media employed were hydrochloric acid at the pH level of 3.0 and phosphate buffers, at pH levels of 6.0 and 8.0, maintained at 37.0 and 25.0 ± 0.5 °C. Results from the analyses showed the ability of MIP polymers to control the release of bromhexine In all cases The imprinted polymers showed a higher affinity for bromhexine and a slower release rate than the non-imprinted polymers. At the pH level of 3.0 and at the temperature of 25 °C, slower release of bromhexine imprinted polymer occurred.

Keywords

Molecularly imprinted polymer Bromhexine Bulk polymerization Drug release Biological systems 

Notes

Acknowledgments

The authors would like to thank Mr. Roghanizad for his technical assistance in experiments.

References

  1. 1.
    Mosbach, K. (1994). Trends Biochem Sci, 19, 9.CrossRefGoogle Scholar
  2. 2.
    Komiyama, M., Takeuch, T., Mukawa, T., & Asanuma, H. (2003). Molecular imprinting. Weinheim: Wiley.Google Scholar
  3. 3.
    Bartsch, R. A., & Maeda, M. (1998). Molecular and ionic recognition with imprinted polymers, ACS Symposium Series 703. Washington, DC: American Chemical Society.CrossRefGoogle Scholar
  4. 4.
    Sellergen, B. (2001). Molecular imprinted polymers. Amsterdam, The Netherlands: Elsevier.Google Scholar
  5. 5.
    Takeuchi, T., & Haginaka, J. (1999). Separation and sensing based on molecular recognition using molecularly imprinted polymers. J Chromatogr B, 728, 1.CrossRefGoogle Scholar
  6. 6.
    Haupt, K., & Mosbach, K. (2000). Molecularly imprinted polymers and their use in biomimetic sensors. Chem Rev, 100, 2495.CrossRefGoogle Scholar
  7. 7.
    Ho, K. C., Yeh, W. M., Tung, T. S., & Liao, J. Y. (2005). Amperometric detection of morphine based on poly(3, 4-ethylenedioxythiophene) immobilized molecularly imprinted polymer particles prepared by precipitation polymerization. Anal Chim Acta, 542, 90.CrossRefGoogle Scholar
  8. 8.
    Javanbakht, M., Eynollahi Fard, S., Mohammadi, A., Abdouss, M., Ganjali, M. R., Norouzi, P., et al. (2008). Molecularly imprinted polymer based potentiometric sensor for the determination of hydroxyzine in tablets and biological fluids. Anal Chim Acta, 612, 65.CrossRefGoogle Scholar
  9. 9.
    Vallano, P. T., & Remcho, V. T. (2000). Highly selective separations by capillary electrochromatography: molecular imprint polymer sorbents. J Chromatogr A, 887, 125.CrossRefGoogle Scholar
  10. 10.
    Kamal, A., Kumar, B. A., Arifuddin, M., & Dastidar, S. G. (2003). Synthesis of 4β-amido and 4β-sulphonamido analogues of podophyllotoxin as potential antitumour agents. Bioorg Med Chem, 11, 5135.CrossRefGoogle Scholar
  11. 11.
    Puoci, F., Curcio, M., Cirillo, G., Lemma, F., Spizzirri, U. G., & Picci, N. (2008). Molecularly imprinted solid-phase extraction for cholesterol determination in cheese products. Food Chem, 106, 836.CrossRefGoogle Scholar
  12. 12.
    Chen, W., Han, D. K., Ahn, K. D., & Kim, J. M. (2002). Molecularly imprinted polymers having amidine and imidazole functional groups as an enzyme-mimetic catalyst for ester hydrolysis. Macromol Res, 10, 122–126.Google Scholar
  13. 13.
    Suedee, R., Srichana, T., & Martin, G. (2000). Evaluation of matrices containing molecularly imprinted polymers in the enantioselective-controlled delivery of β-blockers. J Control Release, 66, 135–147.CrossRefGoogle Scholar
  14. 14.
    Sambe, H., Hoshina, K., Moadel, R., Wainer, W., & Haginaka, J. (2006). Uniformly-sized, molecularly imprinted polymers for nicotine by precipitation polymerization. J Chromatogr A, 1134, 88–94.CrossRefGoogle Scholar
  15. 15.
    Allender, C. J., Richardson, C., Woodhouse, B., Heard, C. M., & Brain, K. R. (2000). Pharmaceutical applications for molecularly imprinted polymers. Int J Pharm, 195, 39–43.CrossRefGoogle Scholar
  16. 16.
    Alvarez-Lorenzo, C., & Concheiro, A. (2006). Molecularly imprinted materials as advanced excipients for drug delivery systems. Biotechnol Annu Rev, 12, 225–268.CrossRefGoogle Scholar
  17. 17.
    Hiratani, H., & Alvarez-Lorenzo, C. (2002). Timolol uptake and release by imprinted soft contact lenses made of N,N-diethylacrylamide and methacrylic acid. J Control Release, 83, 223–230.CrossRefGoogle Scholar
  18. 18.
    Alvarez-Lorenzo, C., & Concheiro, A. (2004). Molecularly imprinted polymers for drug delivery. J Chromatogr B, 804, 231–245.CrossRefGoogle Scholar
  19. 19.
    Alvarez-Lorenzo, C., Yanez, F., Barreiro-Iglesias, R., & Concheiro, A. (2006). Imprinted soft contact lenses as norfloxacin delivery systems. J Control Release, 113, 236–244.CrossRefGoogle Scholar
  20. 20.
    Sellergren, B., & Allender, C. J. (2005). Molecularly imprinted polymers: a bridge to advanced drug delivery. Adv Drug Deliv Rev, 57, 1733–1741.CrossRefGoogle Scholar
  21. 21.
    Turchan, M., Jara-Ulloa, P., Bollo, S., Nunez-Vergara, L. J., Squella, J. A., & Alvarez-Lueje, A. (2007). Voltammetric behaviour of bromhexine and its determination in pharmaceuticals. Talanta, 73, 913.CrossRefGoogle Scholar
  22. 22.
    Suedee, R., Srichana, T., & Rattananont, T. (2002). Enantioselective release of controlled delivery granules based on molecularly imprinted polymers. Drug Deliv, 9, 19–30.CrossRefGoogle Scholar
  23. 23.
    Moffat, A. C. (2004). Clarkes analysis of drugs and poisons in pharmaceuticals, Vol. 2 (3rd ed.). London, UK: Pharmaceutical Press.Google Scholar
  24. 24.
    Guyot, A., Sherrington, D. C., & Hodge, P. (1989). Synthesis and separations using functional polymers (pp. 1–36). New York, NY: Wiley.Google Scholar
  25. 25.
    Lloyd, L. (1991). Rigid macroporous copolymers as stationary phases in high-performance liquid chromatography. J Chromatogr A, 544, 201.CrossRefGoogle Scholar
  26. 26.
    Spivak, D. A. (2005). Optimization, evaluation, and characterization of molecularly imprinted polymers. Adv Drug Deliv Rev, 57, 1779–1794.CrossRefGoogle Scholar
  27. 27.
    Rachkov, A., & Minoura, N. (2000). Recognition of oxytocin and oxytocin-related peptides in aqueous media using a molecularly imprinted polymer synthesized by the epitope approach. J Chromatogr A, 889, 111.CrossRefGoogle Scholar
  28. 28.
    Panahi, R., Vasheghani-Farahani, E., & Shojaosadati, S. A. (2007). Separation of l-lysine from dilute aqueous solution using molecular imprinting technique. Biochem Eng J, 35, 352–356.CrossRefGoogle Scholar
  29. 29.
    Javanbakht, M., Shaabani, N., & Akbari-Adergani, B. (2009). Novel molecularly imprinted polymers for the selective extraction and determination of metoclopramide in human serum and urine samples using high-performance liquid chromatography. J Chromatogr B, 887, 2537–2544.CrossRefGoogle Scholar
  30. 30.
    Martin, P., Jones, G. R., Stringer, F., & Wilson, I. D. (2003). Comparison of normal and reversed-phase solid phase extraction methods for extraction of b-blockers from plasma using molecularly imprinted polymers. J Anal, 128(128), 345.CrossRefGoogle Scholar
  31. 31.
    Nicholls, I. A. (1997). Combined hydrophobic and electrostatic interaction-based recognition in molecularly imprinted polymers. Recent Res Dev Pure Appl Chem, 1, 133.Google Scholar
  32. 32.
    Shea, K. J., Spivak, D. A., & Sellergren, B. (1993). Imprinted polymer membranes for the selective transport of targeted neutral molecules. J Am Chem Soc, 115, 3368.CrossRefGoogle Scholar
  33. 33.
    Mullet, W. M., Walles, M., Levsen, K., Borlak, J., & Pawliszyn, J. (2004). Multidimensional on-line sample preparation of verapamil and its metabolites by a molecularly imprinted polymer coupled to liquid chromatography–mass spectrometry. J Chromatogr B, 801, 297.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Saman Azodi-Deilami
    • 1
  • Majid Abdouss
    • 1
  • Mehran Javanbakht
    • 1
  1. 1.Department of ChemistryAmirkabir University of TechnologyTehranIran

Personalised recommendations