Sedimentation analysis of potential interactions between mucins and a putative bioadhesive polymer

  • I. Fiebrig
  • S. E. Harding
  • S. S. Davis
Conference paper
Part of the Progress in Colloid & Polymer Science book series (PROGCOLLOID, volume 94)


A potentially fruitful but hitherto relatively unexplored application of the analytical ultracentrifuge is the investigation of interactions in pharmaceutical polymer drug carrier systems. In this study we investigate the interactions of the cationic material chitosan with gastric mucin: 1) The physicochemical properties of gastric mucin and chitosan (highly deacetylated chitosan “Sea Cure + 210”) in solution are summarised; 2) We described how the gastric mucin (from pig) can be purified by a combination of preparative isopycnic density gradient ultracentrifugation and gel chromatography, and how its purity and structural integrity can be checked by analytical isopycnic density gradient ultracentrifugation (on a MSE Centriscan 75 Analytical Ultracentrifuge) and on line GPC/MALLS (gel permeation chromatography coupled on-line to a multi-angle laser light scattering photometer); 3) Using co-sedimentation experiments with the appropriate controls in an XL-A Ultracentrifuge (absorption optics) and an MSE Mk II Analytical Ultracentrifuge (Schlieren optics) a definite interaction between chitosan and pig gastric mucin was demonstrated, with complexes sedimenting faster than 1000 S, depending on the amount of the mucin used.

Key words

Drug delivery bioadhesion chitosan mucin analytical ultracentrifugation 


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  1. 1.
    Anderson MT (1991) The Interaction of Mucous Glycoproteins with Polymeric Materials, Ph.D. thesis, University of Nottingham, EnglandGoogle Scholar
  2. 2.
    Robinson JR (1990) Rationale of bioadhesion/mucoadhesion. In: Gurny R, Junginger HE (eds) Bioadhesion: Possibilities and Future Trends. Wissenschaftliche Verlagsgesellschaft mbH, Stuttgart, pp 13–15Google Scholar
  3. 3.
    Allen A (1981) Structure and function of gastrointestinal mucus. In: Johnson LR (ed) Physiology of the Gastrointestinal Tract by Raven Press, NY, pp 617–639Google Scholar
  4. 4.
    Lehr C-M, Bouwstra JA, Schacht EH, Junginger HE, (1992) In vitro evaluation of mucoadhesive properties of chiotsan and some other natural polymers. Int. J. Pharmaceutics 78:43–48CrossRefGoogle Scholar
  5. 5.
    Allen A (1989) Gastrointestinal mucus. In: Schultz SG, Forte JG, Rauner BB (eds) Physiology of the Gastrointestinal Tract — The GI-System III, American Physiological Society, Bethesda, Maryland, pp 359–382Google Scholar
  6. 6.
    Carstedt I and Sheehan JK (1988) Structure and macromolecular properties of mucus glycoproteins. Monogr. Allergy. Karger Basel, 24:16–24Google Scholar
  7. 7.
    Neutra MR and Forstner JF (1987) Gastrointestinal mucus: Synthesis, secretion and function. In: Johnson LR (ed) Physiology of the Gastrointestinal Trace, 2nd ed. Raven Press, NY, pp 975–1009Google Scholar
  8. 8.
    Silberberg A (1987) A model for mucus glycoprotein structure Biorheology 24:605–614Google Scholar
  9. 9.
    Carlstedt I, Sheehan JK, Corfield AP and Gallagher JT (1985) Mucus glycoproteins. In: A Gel of a Problem, Essays in Biochemistry 20:40–76Google Scholar
  10. 10.
    Allen A (1978) Structure of gastrointestinal mucus glycoprotein and the viscous and gel forming properties of mucus. Br Med Bull 34:28–33Google Scholar
  11. 11.
    Harding SE (1989) The macrostructure of mucus glycoproteins in solution. Adv Carb Chem Biochem 47:345–383CrossRefGoogle Scholar
  12. 12.
    Schauer R. (1992) Sialinsäurereiche Schleime als bioaktive Schmierstoffe. Nachr Chem Tech Lab 40, Nr 11:1227–1231Google Scholar
  13. 13.
    Sandford, PA (1989) Chitosan: Commercial uses and potential applications. In: Skjåk-Braek G, Anthonsen T, Sandford P (eds) Chitin & Chitosan, pp 51–69Google Scholar
  14. 14.
    Dawson MC, Elliot DC, Elliot WH, Jones KM (1986) Data for Biochemical Research, Clarendon Press Oxford, p. 429Google Scholar
  15. 15.
    Hutton DA, Pearson JP, Allen A, Foster SNE (1990) Mucolysis of the colonic mucus barrier by faecal proteinases: Inhibition by interacting polyacrylate. Clinical Science 78:265–271Google Scholar
  16. 16.
    Errington N, Harding SE, Vårum KM, Illum L (1993) Hydrodynamic characterization of chiotsans varying in degree of acetylation. Int J Biol Macromol 15:113–117CrossRefGoogle Scholar
  17. 17.
    Creeth JM, Bhaskar KR, Horton JR (1977) The separation and characterization of bronchial glycoproteins by density-gradient methods. Biochem J 167:557–569Google Scholar
  18. 18.
    Ifft JB, Vinograd J (1966) The buoyant behaviour of bovine serum mercaptalbumin in salt solutions at equilibrium in the untracentrifuge. II. Net hydration ion binding and solvated molecular weight in various salt solutions. J Phys Chem 70:2814–2822CrossRefGoogle Scholar
  19. 19.
    Creeth JM, Horton JR (1977) Macromolecular distribution near the limits of density-gradient columns, Biochem J 161:449–463Google Scholar
  20. 20.
    Creeth JM, Denborough MA (1970) The use of equilibrium-density-gradient methods for the preparation and characterization of blood-group-specific glycoproteins. Biochem J 117:879–891Google Scholar
  21. 21.
    Wyatt PJ (1992) Combined differential light scattering with various liquid chromatography separation techniques In: Harding SE, Sattelle DB, Bloomfield VA (eds) Laser Light Scattering in Biochemistry. The Royal Society of Chemistry, London, pp 35–58Google Scholar
  22. 22.
    King DJ, Byron OD, Mountain A, Waeir N, Harvey A, Iawson ADG, Proudfoot KA, Baldock D, Harding SE, Yaaranton GT, Owens RJ (1993) Expressions, purification and characterization of B72.3 Fv fragments. Biochem J 290:723–729Google Scholar
  23. 23.
    Creeth JM, Bhaskar KR, Horton JR (1977) The separation and characterization of bronchial glycoproteins by density gradient methods. Biochem J 167:557–569Google Scholar
  24. 24.
    Harding SE, Creeth JM (1983) Polyelectrolyte behaviour in mucus glycoproteins. Biochim et Biophys Acta 746:114–119Google Scholar

Copyright information

© Dr. Dietrich Steinkopff Verlag GmbH & Co. KG 1994

Authors and Affiliations

  • I. Fiebrig
    • 1
    • 2
  • S. E. Harding
    • 1
  • S. S. Davis
    • 2
  1. 1.National Centre for Macromolecular Hydrodynamics, School of Agriculture, Sutton BoningtonUniversity of NottinghamEngland
  2. 2.Department of Pharmaceutical SciencesNottinghamUnited Kingdom

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