Pharmaceutical Research

, Volume 13, Issue 12, pp 1838–1845

Gastrointestinal Uptake of Biodegradable Microparticles: Effect of Particle Size

  • Manisha P. Desai
  • Vinod Labhasetwar
  • Gordon L. Amidon
  • Robert J. Levy


Purpose. To investigate the effect of microparticle size on gastrointestinal tissue uptake.

Methods. Biodegradable microparticles of various sizes using polylactic polyglycolic acid (50:50) co-polymer (100 nm, 500 nm, 1µm, and 10 µm) and bovine serum albumin as a model protein were formulated by water-in-oil-in-water emulsion solvent evaporation technique. The uptake of microparticles was studied in rat in situ intestinal loop model and quantitatively analyzed for efficiency of uptake.

Results. In general, the efficiency of uptake of 100 nm size particles by the intestinal tissue was 15–250 fold higher compared to larger size microparticles. The efficiency of uptake was dependent on the type of tissue, such as Peyer's patch and non patch as well as on the location of the tissue collected i.e. duodenum or ileum. Depending on the size of microparticles, the Peyer's patch tissue had 2–200 fold higher uptake of particles than the non-patch tissue collected from the same region of the intestine. Histological evaluation of the tissue sections demonstrated that 100 nm particles were diffused throughout the submucosal layers while the larger size nano/microparticles were predominantly localized in the epithelial lining of the tissue.

Conclusions. There is a microparticle size dependent exclusion phenomena in the gastrointestinal mucosal tissue with 100 nm size particles showing significantly greater tissue uptake. This has important implications in designing of nanoparticle-based oral drug delivery systems, such as an oral vaccine system.

oral drug delivery nanoparticles Peyer's patches size exclusion vaccine 


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  1. 1.
    P. Couvreur, B. Kante, M. Roland and P. Speiser. J. Pharm. Sci. 68(12):1521–1524 (1979).Google Scholar
  2. 2.
    P. Couvreur, V. Lenaerts, D. Leyh, P. Guiot and M. Roland. In Microspheres and Drug Therapy. Pharmacuticals, Immunological and Medical Aspects. Edited by S. S. Davis, L. Illum, J. G. McVie and E. Tomlinson., Elsevier Science Publishers B. V. 103–115 (1984).Google Scholar
  3. 3.
    J. Kreuter. Inter. J. Pharm. 14:43–58 (1983).Google Scholar
  4. 4.
    L. Illum, S. S. Davis, R. H. Muller, E. Mak and P. West. Life Sci. 40:367–374 (1987).Google Scholar
  5. 5.
    P. Maincent, R. Le Verge, P. A. Sado, P. Couvreur and J. P. Devissaguet. J. Pharm. Sci. 75:955–958 (1986).Google Scholar
  6. 6.
    P. A. Kramer and T. Burnstein. Life Sci. 19:515–520 (1976).Google Scholar
  7. 7.
    J. J. Marty, R. C. Oppenheim and P. P. Speiser. Pharm. Acta Helv. 53:17–23 (1978).Google Scholar
  8. 8.
    C. M. Adeyeye, J. D. Bricker, V. D. Vilivalam and W. I. Smith. Pharm. Res. 13:784–793 (1996).Google Scholar
  9. 9.
    J. Mestecky, Z. Moldoveanu, M. Novak, W. Q. Huang, R. M. Gilley, J. K. Staas, D. Schafer and R. W. Compans. J. Control. Rel. 28:131–141 (1994).Google Scholar
  10. 10.
    C. A. Gilligan and A. L. Wan Po. Inter. J. Pharm. 75:1–24 (1991).Google Scholar
  11. 11.
    D. T. O'Hagan, K. J. Palin and S. S. Davis. CRC Critical Reviews in Therapeutic Drug Carrier Systems. 4:197–220 (1987).Google Scholar
  12. 12.
    H. O. Alpar, W. N. Field, R. Hyde and D. A. Lewis, J. Pharm. Pharmacol. 41:194–196 (1989).Google Scholar
  13. 13.
    M. E. LeFevre, J. W. Vanderhoff, J. A. Laissue and D. D. Joel. Experientia.. 34:120–122 (1978).Google Scholar
  14. 14.
    A. T. Florence and P. U. Jani. In Pharmaceutical Particulate Carriers. Therapeutic Application. Edited by Alain Rolland, Marcel Dekker Inc. 61:65–108 (1993).Google Scholar
  15. 15.
    J. Pappo and T. H. Ermak. Clin. Exp. Immunol. 76:144–148 (1989).Google Scholar
  16. 16.
    E. Sanders and C. T. Ashworth. Exp. Cell Res. 22:137–145 (1961).Google Scholar
  17. 17.
    P. Jani, G. W. Halbert, J. Langridge and A. T. Florence. J. Pharm. Pharmacol. 41:809–812 (1989).Google Scholar
  18. 18.
    P. Jani, G. W. Halbert, J. Langridge and A. T. Florence. J. Pharm. Pharmacol. 42:821–826 (1990).Google Scholar
  19. 19.
    D. S. Cox and M. A. Taubman. Int. Archs Allergy Appl. Immun. 75:126–131 (1984).Google Scholar
  20. 20.
    O. Strannegard and A. Yurchision. Int. Arch. Allergy. 35:579–590 (1969).Google Scholar
  21. 21.
    J. R. McGhee, J. Mestecky, M. T. Dertzbaugh, J. H. Eldridge, M. Hirasawa and H. Kiyono. Vaccine 10:75–88 (1992).Google Scholar
  22. 22.
    M. E. LeFevre and D. D. Joel. In Intestinal Toxicology. Edited by C. M. Schiller. Raven Press. 45–56 (1984).Google Scholar
  23. 23.
    J. H. Eldridge, J. K. Staas, J. A. Meulbroek, J. R. McGhee, T. R. Tice and R. M. Gilley. Mol. Immunol. 28:287–294 (1991).Google Scholar
  24. 24.
    J. P. Ebel. Pharm. Res. 7:848–451 (1990).Google Scholar
  25. 25.
    A. M. Hillery, P. U. Jani and A. T. Florence. J. Drug Targetting. 2:151–156 (1994).Google Scholar
  26. 26.
    H. Tomizawa, Y. Aramaki, Y. Fujii, T. Hara, N. Suzuki, K. Yachi, H. Kikuchi and S. Tsuchiya. Pharm. Res. 10:549–552 (1993).Google Scholar
  27. 27.
    R. H. Muller. In Colloidal carriers for controlled drug delivery and targeting. CRC Press, Boston. 43–45 (1991).Google Scholar
  28. 28.
    J. H. Eldridge, C. J. Hammond, J. A. Muelbroek, J. K. Staas, R. M. Gilley and T. R. Tice. J. Control. Rel. 11:205–214 (1990).Google Scholar
  29. 29.
    C. Damge, C. Michel, M. Aprahamian, P. Couvreur and J. P. Devissaguet. J. Control. Rel. 13:233–237 (1990).Google Scholar
  30. 30.
    M. Aprahamian, C. Michel, W. Humbert, J. P. Devissaguet and C. Damge. Bio. Cell. 61:69–74 (1987).Google Scholar

Copyright information

© Plenum Publishing Corporation 1996

Authors and Affiliations

  • Manisha P. Desai
    • 1
    • 2
  • Vinod Labhasetwar
    • 1
    • 2
  • Gordon L. Amidon
    • 2
  • Robert J. Levy
    • 1
    • 2
  1. 1.Division of Pediatric CardiologyUniversity of MichiganAnn Arbor
  2. 2.College of PharmacyUniversity of MichiganAnn Arbor

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