Skip to main content

Advertisement

Journal for Biophysical Chemistry

Biointerphases Cover Image

Enhancement of poly (ethylene glycol) mucoadsorption by biomimetic end group functionalization

Article metrics

Abstract

Poly(ethylene glycol) (PEG) is widely used in the pharmaceutical, biotechnology, and medical device industries. Although PEG is a biocompatible polymer that has enjoyed widespread use in drug delivery technology, it is not considered adhesive toward mucosal tissue. Here the authors describe a simple approach to enhancing mucoadsorption of PEG polymers through end group functionalization with the amino acid 3,4-dihydroxyphenyl-l-alanine (DOPA). Using a variety of surface analytical techniques, the authors show that a four-armed poly(ethylene glycol) polymer functionalized with a single DOPA residue at the terminus of each arm (PEG-(DOPA)4 adsorbed strongly to surface immobilized mucin. Successful mucoadsorption of PEG-(DOPA)4 across several pH values ranging from 4.5 to 8.5 was demonstrated, and control experiments with unfunctionalized four-arm PEG demonstrated that mucoadsorption of PEG-(DOPA)4 is due largely to the presence of DOPA end groups. This conclusion was confirmed with single molecule atomic force microscopy experiments that revealed a surprisingly strong interaction force of 371±93 pN between DOPA and adsorbed mucin. Direct comparisons with known mucoadhesive polymers revealed that PEG-(DOPA)4 was equal to or more adsorptive to immobilized mucin than these existing mucoadhesive polymers. In addition to demonstrating significant enhancement of mucoadhesive properties of PEG by DOPA functionalization, this study also introduced a new simple approach for rapid screening of mucoadhesive polymers.

References

  1. 1

    N. A. Peppas and Y. Huang, Adv. Drug Delivery Rev. 56, 1675 (2004).

  2. 2

    A. Bernkop-Schnurch, Adv. Drug Delivery Rev. 57, 1553 (2005).

  3. 3

    A. Ludwig, Adv. Drug Delivery Rev. 57, 1595 (2005).

  4. 4

    M. I. Ugwoke, R. U. Agu, N. Verbeke, and R. Kinget, Adv. Drug Delivery Rev. 57, 1640 (2005).

  5. 5

    N. Salamat-Miller, M. Chittchang, and T. P. Johnston, Adv. Drug Delivery Rev. 57, 1666 (2005).

  6. 6

    C. Valenta, Adv. Drug Delivery Rev. 57, 1692 (2005).

  7. 7

    V. Grabovac, D. Guggi, and A. Bernkop-Schnurch, Adv. Drug Delivery Rev. 57, 1713 (2005).

  8. 8

    J. Cleary, L. Bromberg, and E. Magner, Langmuir 20, 9755 (2004).

  9. 9

    V. R. Sinha, A. K. Singla, S. Wadhawan, R. Kaushik, R. Kumria,K. Bansal, and S. Dhawan, Int. J. Pharm. 274, 1 (2004).

  10. 10

    S. Kockisch, G. D. Rees, S. A. Young, J. Tsibouklis, and J. D. Smart, Int. J. Pharm. 276, 51 (2004).

  11. 11

    X. Zhu, J. DeGraaf, F. M. Winnik, and D. Leckband, Langmuir 20, 10648 (2004).

  12. 12

    K. Kafedjiiski, M. Werle, F. Foger, and A. Bernkop-Schnurch, J. Drug Delivery Sci. and Tech. 15, 411 (2005).

  13. 13

    K. Maculotti, I. Genta, P. Perugini, M. Imam, A. Bernkop-Schnurch, and F. Pavanetto, J. Microencapsul. 22, 459 (2005).

  14. 14

    J. D. Smart, I. W. Kellaway, and H. E. C. Worthington, J. Pharm. Pharmacol. 36, 295 (1984).

  15. 15

    A. De Ascentiis, J. L. deGrazia, C. N. Bowman, P. Colombo, and N. A. Peppas, J. Controlled Release 33, 197 (1995).

  16. 16

    N. A. Peppas and A. G. Mikos, STP Pharma Sciences 5, 187 (1989).

  17. 17

    H. Takeuchi, J. Thongborisute, Y. Matsui, H. Sugihara, H. Yamamoto, and Y. Kawashima, Adv. Drug Delivery Rev. 57, 1583 (2005).

  18. 18

    Y. Huang, W. Leobandung, A. Foss, and N. A. Peppas, J. Controlled Release 65, 63 (2000).

  19. 19

    M. P. Deacon, S. S. Davis, J. H. Waite, and S. E. Harding, Biochemistry 37, 14108 (1998).

  20. 20

    J. Schnurrer and C. M. Lehr, Int. J. Pharm. 141, 251 (1996).

  21. 21

    B. P. Lee, J. L. Dalsin, and P. B. Messersmith, Biomacromolecules 3, 1038 (2002).

  22. 22

    K. Huang, B. P. Lee, D. R. Ingram, and P. B. Messersmith, Biomacromolecules 3, 397 (2002).

  23. 23

    J. H. Waite, Int. J. Adhes. Adhes. 7, 9 (1987).

  24. 24

    J. H. Waite, Ann. N.Y. Acad. Sci. 875, 301 (1999).

  25. 25

    A. A. Ooka and R. L. Garrell, Biopolymers 57, 92 (2000).

  26. 26

    J. N. Hilfiker and R. A. Synowicki, Solid State Technol. 41, 101 (1998).

  27. 27

    J. Voros, J. J. Ramsden, G. Csucs, I. Szendro, S. M. D. Paul, M. Textor, and N. D. Spencer, Biomaterials 23, 3699 (2002).

  28. 28

    J. A. d. Feijter, J. Benjamins, and F. A. Veer, Biopolymers 17, 1759 (1978).

  29. 29

    H. Lee, N. F. Scherer, and P. B. Messersmith, Proc. Natl. Acad. Sci. U.S.A. 103, 12999 (2006).

  30. 30

    J. L. Hutter and J. Bechhoefer, Rev. Sci. Instrum. 64, 1868 (1993).

  31. 31

    L. Shi and K. D. Caldwell, J. Colloid Interface Sci. 224, 372 (2000).

  32. 32

    J. Juna, J.-H. Shina, and M. Dhayal, Appl. Surf. Sci. 252, 3871 (2005).

  33. 33

    U. Dammer, O. Popescu, P. Wagner, D. Anselmetti, H.-J. Guntherodt, and G. N. Misevic, Science 267, 1173 (1995).

  34. 34

    B. Lee, J. L. Dalsin, and P. B. Messersmith, in Biological Adhesives, A. M. Smith and J. A. Callow (Springer-Verlag, Berlin, 2006), pp 257–278.

  35. 35

    J. H. Waite, N. H. Andersen, S. Jewhurst, and C. Sun, J. Adhes. 81, 1 (2005).

  36. 36

    J. Perez-Vilar and R. L. Hill, J. Biol. Chem. 274, 31751 (1999).

  37. 37

    W. Jiang, D. Gupta, D. Gallagher, S. Davis, and V. P. Bhavanandan, Eur. J. Biochem. 267, 2208 (2000).

  38. 38

    M. Grandbois, M. Beyer, M. Rief, H. Clausen-Schaumann, and H. E. Gaub, Science 283, 1727 (1999).

  39. 39

    T. Sulchek, R. W. Friddle, and A. Noy, Biophys. J. 90, 4686 (2006).

  40. 40

    T. A. Sulchek et al., Proc. Natl. Acad. Sci. U.S.A. 102, 16638 (2005).

Download references

Author information

Correspondence to Phillip B. Messersmith.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Catron, N.D., Lee, H. & Messersmith, P.B. Enhancement of poly (ethylene glycol) mucoadsorption by biomimetic end group functionalization. Biointerphases 1, 134–141 (2006) doi:10.1116/1.2422894

Download citation