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.
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REFERENCES
F. Verzar. Absorption from the Intestine. Longmans, Green and Co., London, 1936.
G. Volkheimer and F. H. Schulz, Digestion 1:213–218 (1968); see also G. Volkheimer. Adv. Pharmacol. Chemother., 14:163–187 (1977).
P. U. Jani. G. W. Halbert, J. Langridge, and A. T. Florence. J. Pharmacol. 41:809–812 (1989).
J. E. O'Mullane, P. Artursson, and E. Tomlinson. Ann N.Y. Acad. Sci. 507:117–128 (1987).
S. S. Davis. Bulletin Technique Gattefossé, No 86:9–14 (1993).
S. S. Davis. (Book review), TIPS 15:64 (1994).
I. R. Sanderson and W. A. Walker. Gastroenterology 104:622–639 (1993).
W. A. Walker. Ann. Allergy 59:7–16 (1974).
J. Pappo and R. T. Mahlman. Immunology 78:505–507 (1993).
P. Sundaram, W. Xiao, and J. L. Brandsma. Nucleic Acids Res. 24:1375–1377 (1996).
G. Cevc, A. Shätzlein, and G. Blume. J. Control. Rel. 36:3–16 (1995).
R. D. Pontefract and H. M. Cunningham. Nature 243:352–353 (1973).
J. G. Collee. Lancet 347:917–918 (1996).
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).
S. N. Sullivan, Lancet 336:1096–1097 (1990).
N. A. Shepherd, P. R. Crocker, A. P. Smith, and D. A. Levison. Hum. Pathol. 18:50–54 (1987).
J. J. Powell, C. C. Ainley, R. S. J. Harvey, I. M. Mason et al., Gut 38:390–395.
P. U. Jani, D. E. McCarthy, and A. T. Florence. Int. J. Pharm. 105:157–168 (1994).
A. C. Wotherspoon, C. Ortiz-Hidalgo, M. R. Falzon, and P. G. Isaacson. Lancet 338:1175–1176 (1991).
T. T. MacDonald and J. O. Spencer in (ed) R. V. Heatley, Gastrointestinal and Hepatic Immunology. Cambridge University Press: Cambridge, 1994.
M. A. Jepson, M. A. Clark, N. L. Simmons, and B. H. Hirst. Histochemistry, 100:441–447 (1993).
R. D. Berg and A. W. Garlington. Infect. Immunol. 23:403–411 (1979).
P. C. Sedman, J. Macfie, P. Sagar, C. J. Mitchell, J. May, B. Mancey-Jones, and D. Johnstone. Gastroenterology 107:643–649 (1994).
E. A. Deitch. Arch. Surg. 124:699–701 (1989).
N. S. Ambrose, M. Johnson, D. W. Burdon, and M. R. B. Keighley. Br. J. Surg. 71:623–625.
C. L. Wells, R. P. Jechorek, S. B. Olmsted, and S. L. Erlandsen.
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).
D. J. Keljo, D. G. Butler, and J. R. Hamilton. Gastroenterology 88:998–1004 (1985).
J. Kreuter. Adv. Drug Del. Rev. 7:71–86 (1991).
A. T. Florence and P. U. Jani. in A. Rolland (ed.) Pharmaceutical Particulate Carriers. Marcel Dekker, New York, 1993.
D. T. O'Hagan. Adv. Drug Del. Rev. 5:265–285 (1990).
E. C. Lavelle, S. Sharif, N. W. Thomas, J. Holland, and S. S. Davis. Adv. Drug Dev. Rev. 18:5–22 (1995).
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.
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.
P. U. Jani, G. W. Halbert, J. Langridge, and A. T. Florence. J. Pharm. Pharmacol. 42:821–826 (1990).
P. U. Jani, A. T. Florence, and D. E. McCarthy. Int. J. Pharm. 84:245–252 (1992).
A. M. Hillery, P. U. Jani, and A. T. Florence. J. Drug Targeting 2:151–156 (1994).
N. Hussain, PhD Thesis, University of London, 1996; N. Hussain, P. U. Jani and A. T. Florence, Pharm. Res., in press.
A. T. Florence, A. M. Hillery, N. Hussain, and P. U. Jani. J. Drug Targeting 3:65–70 (1995).
A. M. Hillery and A. T. Florence. Int. J. Pharm. 132:123–130 (1996).
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).
M. K. Pratten and J. B. Lloyd. Biochim. Biophys. Acta 881:307–313 (1986).
H. Ayhan, A. Tuncel, N. Bor, and E. Piskin. J. Biomater. Sci. Polymer Edn. 7:329–342 (1995).
S. Rudt and R. H. Müller. J. Control. Rel. 25:51–59 (1993).
M. P. Desai, V. Labhasetwar, G. L. Amidon, and R. J. Levy. Pharm. Res., 13:1838–1845.
M. E. LeFevre, J. W. Vanderhoff, J. A. Laisse, and D. D. Joel. Experientia 34:120–122 (1978).
J. P. Ebel, Pharm. Res. 7:848–851 (1990).
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).
P. Couvreur and F. Puisieux. Adv. Drug Del. Rev. 10:141–162 (1993).
A. M. Le Ray, M. Vert, J. C. Gautier, and J. P. Benoît. Int. J. Pharm. 106:201–211 (1994).
M. Nefzger, J. Kreuter, R. Voges, E. Liehl, and R. Czok. J. Pharm. Sci. 73:1309–1311 (1984).
M. Kukan, V. Koprda, Š. Bezek, J. Kalal, J. Labsky, and T. Trnovec. Pharmazie 46:37–39 (1991).
L. Simon, G. Shine, and A. D. Dayan. J. Drug Targeting, 3:217–219 (1995).
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).
T. H. Ermak, E. P. Dougherty, H. R. Bhagat, Z. Kabok, and J. Pappo. Cell Tissue Res. 279:433–436 (1995).
A. M. Hillery, I. Toth, and A. T. Florence. J. Control. Rel. 41:271–281 (1996).
A. M. Hillery, I. Toth, and A. T. Florence. J. Control. Rel. 42:65–73 (1996).
A. M. Hillery, I. Toth, and A. T. Florence, Pharm. Sci. 2:281–293 (1996).
D. S. Deshmuck, W. D. Bear, and H. Brockerhoff. Life Sci. 28:239–242 (1990).
Y. Aramaki, H. Tomizawa, T. Hara, K. Yachi, H. Kikuchi, and S. Tsuchiya. Pharm. Res. 10:1228–1231 (1993).
H. Chen, V. Torchillin, and R. Langer. J. Control. Rel. 42:263–272 (1996).
S. Gould-Fogerite and R. J. Mannino. J. Liposome Res. 6:357–379 (1996).
D. A. Tomalia, A. M. Naylor, and W. A. Goddard. Angew. Chemie. Int. Edn. 29:138–175 (1990).
T. Sakthivel, A. T. Florence, and I. Toth. Pharm. Res. (Suppl.) 13:S-281 (1996).
L. A. Sternson, Ann. N.Y. Acad. Sci. 507:19–21 (1987).
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.
J. Pappo, T. H. Ermar, and H. T. Steger, Immunol. 73:277 (1991).
H. Chen, V. Torchillin, and R. Langer. Pharm. Res. 13:1378–1383 (1996).
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.
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).
E. Palomina. Adv. Drug Del. Rev. 13:311–323 (1994).
M. N. Jones. Adv. Drug Del. Rev. 13:215–250 (1994).
K. Matsuno, T. Schaffner, H. A. Gerber, C. Ruchti, M. W. Hess, and R. E. S. Cottier. J. Reticuloendothelial Soc. 33:263–273 (1983).
N. Hussain and A. T. Florence. Pharm. Res., in press.
N. Hussain and A. T. Florence, to be published; see H. Hussain PhD Thesis, School of Pharmacy. University of London 1995.
N. Hussain. P. U. Jani, and A. T. Florence. Proc. Int. Symp. Control. Rel. Bioact. Mater. 21:29–30 (1994).
J. M. Irache, C. Durrer, D. Duchêne, and G. Ponchel. Pharm. Res. 13:1716–1719 (1996).
M. A. Jepson, N. L. Simmons, D. T. O'Hagan, and B. H. Hirst. J. Drug Targeting 1:245–249 (1993).
M. A. Jepson, C. M. Mason, M. A. Clark, N. L. Simmons, and B. H. Hirst. J. Drug Targeting 3:75–77 (1995).
T. C. Savidge and A. Shmakova. J. Drug Targeting 3:71–74 (1995).
N. Hussain and A. T. Florence. J. Control. Rel. 41:S3–S4 (1996).
R. R. Isberg and S. Falkow, Nature 317:262–264 (1985).
G. V. B. Young, S. Falkow, and G. K. Schoolnik. J. Cell. Biol. 116:197–207 (1992).
G. Tran van Nhieu and R. R. Isberg J. Biol. Chem. 266:24367–24375 (1991).
P. U. Jani, T. Nomura, F. Yamashita, Y. Takakura, A. T. Florence, and M. Hashida. J. Drug Targeting 4:87–93 (1996).
J. W. Thom and P. G. Debenedetti, J. Aerosol Sci. 22:555–584 (1991).
E. Merisko-Liversidge, P. Sarpotdar, J. Bruno, S. Hajj et al., Pharm. Res. 13:272–278 (1996).
S. M. C. Newton, C. O. Jacob, and B. A. D. Stocker. Science 244:70–72 (1989).
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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
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DOI: https://doi.org/10.1023/A:1012029517394