Skip to main content
SpringerLink
Log in

Size-Dependent Bioadhesion of Micro- and Nanoparticulate Carriers to the Inflamed Colonic Mucosa

  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

Purpose. The size-dependent deposition of microparticles and nanoparticles after oral administration to rats using an experimental model colitis was examined. Local delivery of an entrapped drug could reduce side effects and would be a distinct improvement compared with existing colon delivery devices.

Methods. Ulcerative colitis was induced in Lewis rats with trinitrobenzenesulfonic acid. Fluorescent polystyrene particles with a size of 0.1, 1, or 10 μm were administered for 3 days. The animals then were sacrificed and their guts resected. Particle distribution in the colon was imaged by confocal laser scanning microscopy and quantified by fluorescence spectrophotometry.

Results. In the inflamed tissue, an increased adherence of particles was observed at the thicker mucus layer and in the ulcerated regions. A size dependency of the deposition was found, and an increased number of attached particles to the colon was determined compared with the control group. For 10-μm particles, only fair deposition was observed (control group: 1.4 ± 0.6%; colitis: 5.2 ± 3.8% of administered particle mass). One-micrometer particles showed higher binding (control group: 2.0 ± 0.8%; colitis: 9.1 ± 4.2%). Highest binding was found for 0.1-μm particles (control group: 2.2 ± 1.6%; colitis: 14.5 ± 6.3%). The ratio of colitis/control deposition increased with smaller particle sizes.

Conclusions. The use of submicron-sized carriers holds promise for the targeted delivery of drugs to the inflamed colonic mucosal areas in inflammatory bowel disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. A. McLeod, D. R. Friend, and T. N. Tozer. Glucocorticoid-dextran conjugates as potential prodrugs colon-specific delivery: Hydrolysis in rat gastrointestinal tract contents. J. Pharm. Sci. 83:1284-1288 (1994).

    Google Scholar 

  2. R. Fedorak, B. Haeberlin, L. R. Empey, N. Cui, H. Nolen III, L. D. Jewell, and D. R. Friend. Colonic delivery of dexamethasone from a prodrug accelerates healing of colitis in rats without adrenal suppression. Gastroenterology 108:1688-1699 (1995).

    Google Scholar 

  3. U. Klotz. Clinical pharmacokinetics of sulphasalazine, its metabolites and other prodrugs of 5-aminosalicylic acid. Clin. Pharmacokinet. 10:285-302 (1985).

    Google Scholar 

  4. S. B. Hanauer. Medical therapy of ulcerative colitis. Lancet 342:412-417 (1993).

    Google Scholar 

  5. P. J. Watts and L. Illum. Colonic drug delivery. Drug Dev. Ind. Pharm. 23:893-913 (1997).

    Google Scholar 

  6. R. Kinget, W. Kalala, L. Vervoort, and G. van den Mooter. Colonic drug targeting. J. Drug Target. 6:129-149 (1998).

    Google Scholar 

  7. H. Tozaki, T. Fujita, J. Komoike, S. I. Kim, H. Terashima, S. Muranishi, S. Okabe, and A. Yamamoto. Colon-specific delivery of budenoside with azopolymer-coated pellets: Therapeutic effects of budenoside with a novel dosage form against 2,4,6-trinitrobenzene sulphonic acid-induced colitis in rats. J. Pharm. Pharmacol. 51:257-261 (1999).

    Google Scholar 

  8. F. H. Hardy, S. S. Davis, R. Khosla, and C. S. Robertson. Gastrointestinal transit of small tablets in patients with ulcerative colitis. Int. J. Pharm. 48:79-82 (1988).

    Google Scholar 

  9. P. J. Watts, L. Barrow, K. P. Steed, C. G. Wilson, R. C. Spiller, C. D. Melia, and M. C. Davies. The transit rate of different-sized model dosage forms through the human colon and the effects of a lactulose-induced catharsis. Int. J. Pharm. 87:215-221 (1992).

    Google Scholar 

  10. M. Rodriguez, J. L. Vila-Jato, and D. Torres. Design of a new multiparticulate system for potential site specific and controlled drug delivery to the colonic region. J. Control. Release 55:67-77 (1998).

    Google Scholar 

  11. H. Nakase, K. Okazaki, Y. Tabata, S. Uose, M. Ohana, K. Uchida, Y. Matsushima, C. Kawanami, C. Oshima, Y. Ikada, and T. Chiba. Development of an oral drug delivery system targeting immune-regulating cells in experimental inflammatory bowel disease: A new therapeutic strategy. J. Pharmacol. Exp. Ther. 292:15-21 (2000).

    Google Scholar 

  12. M. C. Allison, S. Cornwall, L. W. Poulter, A. P. Dhillon, and R. E. Pounder. Macrophage heterogeneity in normal colonic mucosa and in inflammatory bowel disease. Gut 29:1531-1538 (1988).

    Google Scholar 

  13. C. A. Seldenrijk, H. A. Drexhage, and S. G. M. Meuwissen. Dentritic cells and scavanger macrophage in chronic inflammatory bowel disease. Gut 30:484-491 (1989).

    Google Scholar 

  14. C. S. Probert, A. Chott, J. R. Turner, L. J. Saubermann, A. C. Stevens, K. Bodinaku, C. O. Elson, S. P. Balk, and R. S. Blumberg. Persistent clonal expansion of peripheral blood CD4+ lymphocytes in chronic inflammatory bowel disease. J. Immunol. 157:3183-3191 (1996).

    Google Scholar 

  15. Y. Tabata, Y. Inoue, and Y. Ikada. Size effect on systemic and mucosal immune responses induced by oral administration of biodegradable microspheres. Vaccine 14:1677-1685 (1996).

    Google Scholar 

  16. H. Pinto-Alphandary, O. Balland, M. Laurent, A. Andremont, F. Puisieux, and P. Couvreur. Intracellular visualization of ampicillin-loaded nanoparticles in peritoneal macrophages infected in vitro with Salmonella typhimurium. Pharm. Res. 11:38-46 (1994).

    Google Scholar 

  17. J. Stein, J. Ries, and K. E. Barrett. Disruption of intestinal barrier function associated with experimental colitis: Possible role of mast cells. Am. J. Physiol. 274:G203-G209 (1998).

    Google Scholar 

  18. G. Yue, F. F. Sun, C. Dunn, K. Yin, and P. Y. K. Wong. The 21-aminosteroid tirilazad mesylate can ameliorate inflammatory bowel disease in rats. J. Pharmacol. Exp. Ther. 276:265-270 (1996).

    Google Scholar 

  19. J. E. Krawisz, P. Sharon, and W. F. Stenson. Quantitative assay for acute intestinal inflammation based on myeloperoxidase activity. Gastroenterology 87:1344-1350 (1984).

    Google Scholar 

  20. T. Yamada, S. Marshall, R. D. Specian, and M. B. Grisham. A comparative analysis of two models of colitis in rats. Gastroenterology 102:1524-1534 (1992).

    Google Scholar 

  21. G. P. Morris, P. L. Beck, M. S. Herridge, W. T. Depew, M. R. Szewczuk, and J. L. Wallace. Hapten-induced model of chronic inflammation and ulceration in the rat colon. Gastroeneterology 96:795-803 (1989).

    Google Scholar 

  22. M. P. Desai, V. Labhasetwar, G. L. Amidon, and R. J. Levy. Gastrointestinal uptake of biodegradable microparticles: Effects of particle size. Pharm. Res. 13:1838-1845 (1996).

    Google Scholar 

  23. P. U. Jani, G. W. Halbert, J. Langridge, and A. T. Florence. The uptake and translocation of latex nanospheres and microspheres after oral administration to rats. J. Pharm. Pharmacol. 41:809-821 (1989).

    Google Scholar 

  24. P. U. Jani, G. W. Halbert, J. Langridge, and A. T. Florence. Nanoparticle uptake by the ratgastrointestinal mucosa: Quantitation and particle size dependency. J. Pharm. Pharmacol. 42:821-826 (1990).

    Google Scholar 

  25. S. Sakuma, R. Sudo, N. Suzuki, H. Kikuchi, M. Akashi, and M. Hayashi. Mucoadhesion of polystyrene nanoparticles having surface hydrophilic polymeric chains in the gastrointestinal tract. Int. J. Pharm. 177:161-172 (1999).

    Google Scholar 

  26. B. Tirosh, and A. Rubinstein. Migration of adhesive and nonadhesive particles in the rat intestine under altered mucus secretion conditions. J. Pharm. Sci. 87:453-456 (1998).

    Google Scholar 

  27. Y. Tabata and Y. Ikada. Phagocytosis of polymer microspheres by macrophages. Adv. Polymer Sci. 94:107-141 (1990).

    Google Scholar 

  28. C. O. Elson, R. B. Sartor, G. S. Tennyson, and R. H. Riddell. Experimental models of inflammatory bowel disease. Gastroenterology 109:1344-1367 (1995).

    Google Scholar 

  29. L. Manil, J. C. Davin, C. Duchenne, C. Kubiak, J. Foidart, P. Couvreur, and P. Mahieu. Uptake of nanoparticles by rat glomerular mesangial cells in vivo and in vitro. Pharm. Res. 11:1160-1165 (1994).

    Google Scholar 

  30. R. Nagashima. Mechanisms of action of sulcrafate. J. Clin. Gastroenterol. 3:117-127 (1981).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biopharmacy and Pharmaceutical Technology, Saarland University, Im Stadtwald, 66123, Saarbrücken, Germany

    Alf Lamprecht, Ulrich Schäfer & Claus-Michael Lehr

Authors
  1. Alf Lamprecht
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ulrich Schäfer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Claus-Michael Lehr
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lamprecht, A., Schäfer, U. & Lehr, CM. Size-Dependent Bioadhesion of Micro- and Nanoparticulate Carriers to the Inflamed Colonic Mucosa. Pharm Res 18, 788–793 (2001). https://doi.org/10.1023/A:1011032328064

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1011032328064

Search

Navigation