Skip to main content
SpringerLink
Log in

The Oral Absorption of Micro- and Nanoparticulates: Neither Exceptional Nor Unusual

  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

This mini-review covers some of the historical and recent arguments over the experimental evidence on the uptake by and translocation from the intestinal mucosa of microparticulates after oral administration. It is concluded that there is now no dispute over the fact that this is a normal occurrence. Particulate uptake does take place, not only via the M-cells in the Peyer's patches and the isolated follicles of the gut-associated lymphoid tissue, but also via the normal intestinal enterocytes. Factors affecting uptake include particle size, surface charge and hydrophobicity and the presence or absence of surface ligands. The covalent attachment of lectin or invasin molecules to the surface of carrier particles leads to greater systemic uptake. Whether or not the route can be utilized for the routine administration of therapeutic agents which are not normally absorbed from the gut is not yet proven. Many studies show that 2−3% of the ingested dose of submicron particles can be absorbed. The increasing diversity of carrier systems, which includes dendrimers and liposomes, needs to be exploited fully. More also must be learned about the inter- and intra-subject variability of lymphoid tissue so that appropriate selectivity can be achieved through the design of specific carriers.

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. F. Verzar. Absorption from the Intestine. Longmans, Green and Co., London, 1936.

    Google Scholar 

  2. G. Volkheimer and F. H. Schulz, Digestion 1:213–218 (1968); see also G. Volkheimer. Adv. Pharmacol. Chemother., 14:163–187 (1977).

    Google Scholar 

  3. P. U. Jani. G. W. Halbert, J. Langridge, and A. T. Florence. J. Pharmacol. 41:809–812 (1989).

    Google Scholar 

  4. J. E. O'Mullane, P. Artursson, and E. Tomlinson. Ann N.Y. Acad. Sci. 507:117–128 (1987).

    Google Scholar 

  5. S. S. Davis. Bulletin Technique Gattefossé, No 86:9–14 (1993).

    Google Scholar 

  6. S. S. Davis. (Book review), TIPS 15:64 (1994).

    Google Scholar 

  7. I. R. Sanderson and W. A. Walker. Gastroenterology 104:622–639 (1993).

    Google Scholar 

  8. W. A. Walker. Ann. Allergy 59:7–16 (1974).

    Google Scholar 

  9. J. Pappo and R. T. Mahlman. Immunology 78:505–507 (1993).

    Google Scholar 

  10. P. Sundaram, W. Xiao, and J. L. Brandsma. Nucleic Acids Res. 24:1375–1377 (1996).

    Google Scholar 

  11. G. Cevc, A. Shätzlein, and G. Blume. J. Control. Rel. 36:3–16 (1995).

    Google Scholar 

  12. R. D. Pontefract and H. M. Cunningham. Nature 243:352–353 (1973).

    Google Scholar 

  13. J. G. Collee. Lancet 347:917–918 (1996).

    Google Scholar 

  14. J. R. Casley-Smith, Ann. N.Y. Acad. Sci. 116:803–830 (1964); J. R. Casley-Smith., Quart. J. Exp. Physiol. 49:365–383 (1964).

    Google Scholar 

  15. S. N. Sullivan, Lancet 336:1096–1097 (1990).

    Google Scholar 

  16. N. A. Shepherd, P. R. Crocker, A. P. Smith, and D. A. Levison. Hum. Pathol. 18:50–54 (1987).

    Google Scholar 

  17. J. J. Powell, C. C. Ainley, R. S. J. Harvey, I. M. Mason et al., Gut 38:390–395.

  18. P. U. Jani, D. E. McCarthy, and A. T. Florence. Int. J. Pharm. 105:157–168 (1994).

    Google Scholar 

  19. A. C. Wotherspoon, C. Ortiz-Hidalgo, M. R. Falzon, and P. G. Isaacson. Lancet 338:1175–1176 (1991).

    Google Scholar 

  20. T. T. MacDonald and J. O. Spencer in (ed) R. V. Heatley, Gastrointestinal and Hepatic Immunology. Cambridge University Press: Cambridge, 1994.

    Google Scholar 

  21. M. A. Jepson, M. A. Clark, N. L. Simmons, and B. H. Hirst. Histochemistry, 100:441–447 (1993).

    Google Scholar 

  22. R. D. Berg and A. W. Garlington. Infect. Immunol. 23:403–411 (1979).

    Google Scholar 

  23. P. C. Sedman, J. Macfie, P. Sagar, C. J. Mitchell, J. May, B. Mancey-Jones, and D. Johnstone. Gastroenterology 107:643–649 (1994).

    Google Scholar 

  24. E. A. Deitch. Arch. Surg. 124:699–701 (1989).

    Google Scholar 

  25. N. S. Ambrose, M. Johnson, D. W. Burdon, and M. R. B. Keighley. Br. J. Surg. 71:623–625.

  26. C. L. Wells, R. P. Jechorek, S. B. Olmsted, and S. L. Erlandsen.

  27. E. A. Deitch, L. Ma, W. J. Ma, M. B. Grisham, D. N. Granger, R. D. Specian, and R. D. Berg. J. Clin. Invest. 84:36–42 (1989).

    Google Scholar 

  28. D. J. Keljo, D. G. Butler, and J. R. Hamilton. Gastroenterology 88:998–1004 (1985).

    Google Scholar 

  29. J. Kreuter. Adv. Drug Del. Rev. 7:71–86 (1991).

    Google Scholar 

  30. A. T. Florence and P. U. Jani. in A. Rolland (ed.) Pharmaceutical Particulate Carriers. Marcel Dekker, New York, 1993.

    Google Scholar 

  31. D. T. O'Hagan. Adv. Drug Del. Rev. 5:265–285 (1990).

    Google Scholar 

  32. E. C. Lavelle, S. Sharif, N. W. Thomas, J. Holland, and S. S. Davis. Adv. Drug Dev. Rev. 18:5–22 (1995).

    Google Scholar 

  33. A. T. Florence, A. M. Hillery, N. Hussain, and P. U. Jani. in G. Gregoriadis et al., (ed.) Targeting of Drugs 4, Plenum, New York, pp. 173–181, 1994.

    Google Scholar 

  34. D. T. O'Hagan, N. M. Christy, and S. S. Davis. Particulate and lymphatic drug delivery in W. N. Charman and V. J. Stella (eds.) Lymphatic Transport of Drugs, CRC Press, 1992.

  35. P. U. Jani, G. W. Halbert, J. Langridge, and A. T. Florence. J. Pharm. Pharmacol. 42:821–826 (1990).

    Google Scholar 

  36. P. U. Jani, A. T. Florence, and D. E. McCarthy. Int. J. Pharm. 84:245–252 (1992).

    Google Scholar 

  37. A. M. Hillery, P. U. Jani, and A. T. Florence. J. Drug Targeting 2:151–156 (1994).

    Google Scholar 

  38. N. Hussain, PhD Thesis, University of London, 1996; N. Hussain, P. U. Jani and A. T. Florence, Pharm. Res., in press.

  39. A. T. Florence, A. M. Hillery, N. Hussain, and P. U. Jani. J. Drug Targeting 3:65–70 (1995).

    Google Scholar 

  40. A. M. Hillery and A. T. Florence. Int. J. Pharm. 132:123–130 (1996).

    Google Scholar 

  41. P. G. Jenkins, K. A. Howard, N. W. Blackhall, N. W. Thomas, S. S. Davis, and D. T. O'Hagan. J. Control. Rel. 29:339–350 (1994).

    Google Scholar 

  42. M. K. Pratten and J. B. Lloyd. Biochim. Biophys. Acta 881:307–313 (1986).

    Google Scholar 

  43. H. Ayhan, A. Tuncel, N. Bor, and E. Piskin. J. Biomater. Sci. Polymer Edn. 7:329–342 (1995).

    Google Scholar 

  44. S. Rudt and R. H. Müller. J. Control. Rel. 25:51–59 (1993).

    Google Scholar 

  45. M. P. Desai, V. Labhasetwar, G. L. Amidon, and R. J. Levy. Pharm. Res., 13:1838–1845.

  46. M. E. LeFevre, J. W. Vanderhoff, J. A. Laisse, and D. D. Joel. Experientia 34:120–122 (1978).

    Google Scholar 

  47. J. P. Ebel, Pharm. Res. 7:848–851 (1990).

    Google Scholar 

  48. J. H. Eldridge, C. J. Hammond, J. A. Meulbroek, J. K. Staas, R. M. Gilley, and T. R. Tice. J. Control. Rel. 11:205–214 (1990).

    Google Scholar 

  49. P. Couvreur and F. Puisieux. Adv. Drug Del. Rev. 10:141–162 (1993).

    Google Scholar 

  50. A. M. Le Ray, M. Vert, J. C. Gautier, and J. P. Benoît. Int. J. Pharm. 106:201–211 (1994).

    Google Scholar 

  51. M. Nefzger, J. Kreuter, R. Voges, E. Liehl, and R. Czok. J. Pharm. Sci. 73:1309–1311 (1984).

    Google Scholar 

  52. M. Kukan, V. Koprda, Š. Bezek, J. Kalal, J. Labsky, and T. Trnovec. Pharmazie 46:37–39 (1991).

    Google Scholar 

  53. L. Simon, G. Shine, and A. D. Dayan. J. Drug Targeting, 3:217–219 (1995).

    Google Scholar 

  54. G. M. Hodges, E. A. Carr, R. A. Hazzard, and K. E. Carr. Digest. Dis. Sci. 40:967–975 (1995); G. M. Hodges, E. A. Carr, R. A. Hazzard et al., J. Drug Targeting 3:57–60 (1995).

    Google Scholar 

  55. T. H. Ermak, E. P. Dougherty, H. R. Bhagat, Z. Kabok, and J. Pappo. Cell Tissue Res. 279:433–436 (1995).

    Google Scholar 

  56. A. M. Hillery, I. Toth, and A. T. Florence. J. Control. Rel. 41:271–281 (1996).

    Google Scholar 

  57. A. M. Hillery, I. Toth, and A. T. Florence. J. Control. Rel. 42:65–73 (1996).

    Google Scholar 

  58. A. M. Hillery, I. Toth, and A. T. Florence, Pharm. Sci. 2:281–293 (1996).

    Google Scholar 

  59. D. S. Deshmuck, W. D. Bear, and H. Brockerhoff. Life Sci. 28:239–242 (1990).

    Google Scholar 

  60. Y. Aramaki, H. Tomizawa, T. Hara, K. Yachi, H. Kikuchi, and S. Tsuchiya. Pharm. Res. 10:1228–1231 (1993).

    Google Scholar 

  61. H. Chen, V. Torchillin, and R. Langer. J. Control. Rel. 42:263–272 (1996).

    Google Scholar 

  62. S. Gould-Fogerite and R. J. Mannino. J. Liposome Res. 6:357–379 (1996).

    Google Scholar 

  63. D. A. Tomalia, A. M. Naylor, and W. A. Goddard. Angew. Chemie. Int. Edn. 29:138–175 (1990).

    Google Scholar 

  64. T. Sakthivel, A. T. Florence, and I. Toth. Pharm. Res. (Suppl.) 13:S-281 (1996).

    Google Scholar 

  65. L. A. Sternson, Ann. N.Y. Acad. Sci. 507:19–21 (1987).

    Google Scholar 

  66. S. J. Brett, A. V. Masurov, I. G. Charles, and J. P. Tite. Eur. J. Immunol. 23:1608–1614 (1993). And refs 18, 19 therein.

    Google Scholar 

  67. J. Pappo, T. H. Ermar, and H. T. Steger, Immunol. 73:277 (1991).

    Google Scholar 

  68. H. Chen, V. Torchillin, and R. Langer. Pharm. Res. 13:1378–1383 (1996).

    Google Scholar 

  69. B. Naisbett and J. F. Woodley. Biochem. Soc. Trans. 18:879–880 (1989); idem., Int. J. Pharm. 107:223–230; Int. J. Pharm. 110:127–136; Int. J. Pharm. 114:227–236; Int. J. Pharm. 247–254.

    Google Scholar 

  70. C-M. Lehr, J. A. Bouwstra, W. Kok, A. B. J. Noach, A. G. de Boer, and H. E. Juninger. Pharm. Res. 9:547–553 (1992); C.-M. Lehr and V. H. L. Lee. Pharm. Res. 10:1796–1799 (1993); E. Halfner, J. H. Easson, G. Russell-Jones and C.-M. Lehr. J. Control. Rel. 41:S1 (1996).

    Google Scholar 

  71. E. Palomina. Adv. Drug Del. Rev. 13:311–323 (1994).

    Google Scholar 

  72. M. N. Jones. Adv. Drug Del. Rev. 13:215–250 (1994).

    Google Scholar 

  73. K. Matsuno, T. Schaffner, H. A. Gerber, C. Ruchti, M. W. Hess, and R. E. S. Cottier. J. Reticuloendothelial Soc. 33:263–273 (1983).

    Google Scholar 

  74. N. Hussain and A. T. Florence. Pharm. Res., in press.

  75. N. Hussain and A. T. Florence, to be published; see H. Hussain PhD Thesis, School of Pharmacy. University of London 1995.

  76. N. Hussain. P. U. Jani, and A. T. Florence. Proc. Int. Symp. Control. Rel. Bioact. Mater. 21:29–30 (1994).

    Google Scholar 

  77. J. M. Irache, C. Durrer, D. Duchêne, and G. Ponchel. Pharm. Res. 13:1716–1719 (1996).

    Google Scholar 

  78. M. A. Jepson, N. L. Simmons, D. T. O'Hagan, and B. H. Hirst. J. Drug Targeting 1:245–249 (1993).

    Google Scholar 

  79. M. A. Jepson, C. M. Mason, M. A. Clark, N. L. Simmons, and B. H. Hirst. J. Drug Targeting 3:75–77 (1995).

    Google Scholar 

  80. T. C. Savidge and A. Shmakova. J. Drug Targeting 3:71–74 (1995).

    Google Scholar 

  81. N. Hussain and A. T. Florence. J. Control. Rel. 41:S3–S4 (1996).

    Google Scholar 

  82. R. R. Isberg and S. Falkow, Nature 317:262–264 (1985).

    Google Scholar 

  83. G. V. B. Young, S. Falkow, and G. K. Schoolnik. J. Cell. Biol. 116:197–207 (1992).

    Google Scholar 

  84. G. Tran van Nhieu and R. R. Isberg J. Biol. Chem. 266:24367–24375 (1991).

    Google Scholar 

  85. P. U. Jani, T. Nomura, F. Yamashita, Y. Takakura, A. T. Florence, and M. Hashida. J. Drug Targeting 4:87–93 (1996).

    Google Scholar 

  86. J. W. Thom and P. G. Debenedetti, J. Aerosol Sci. 22:555–584 (1991).

    Google Scholar 

  87. E. Merisko-Liversidge, P. Sarpotdar, J. Bruno, S. Hajj et al., Pharm. Res. 13:272–278 (1996).

    Google Scholar 

  88. S. M. C. Newton, C. O. Jacob, and B. A. D. Stocker. Science 244:70–72 (1989).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Centre for Drug Delivery Research, School of Pharmacy, University of London, London, WC1N 1AX, United Kingdom

    Alexander T. Florence

Authors
  1. Alexander T. Florence
    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

Florence, A.T. The Oral Absorption of Micro- and Nanoparticulates: Neither Exceptional Nor Unusual. Pharm Res 14, 259–266 (1997). https://doi.org/10.1023/A:1012029517394

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1012029517394

Search

Navigation