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Biologically erodable microspheres as potential oral drug delivery systems

Nature volume 386, pages 410–414 (1997)Cite this article

Abstract

Biologically adhesive delivery systems offer important advantages1–5 over conventional drug delivery systems6. Here we show that engineered polymer microspheres made of biologically erodable polymers, which display strong adhesive interactions with gastrointestinal mucus and cellular linings, can traverse both the mucosal absorptive epithelium and the follicle-associated epithelium covering the lymphoid tissue of Peyer's patches. The polymers maintain contact with intestinal epithelium for extended periods of time and actually penetrate it, through and between cells. Thus, once loaded with compounds of pharmacological interest, the microspheres could be developed as delivery systems to transfer biologically active molecules to the circulation. We show that these microspheres increase the absorption of three model substances of widely different molecular size: dicumarol, insulin and plasmid DNA.

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References

  1. Lenaerts, V., Couvreur, P., Grislain, L. & Maincent, P. in Bioadhesive Drug Delivery Systems (eds Lenaerts, V. & Gurny, R.) 93–104 (CRC Press, Boca Raton, FL, 1990).

    Google Scholar 

  2. Peppas, N. A. Hydrogels in Medicine and Pharmacy (CRC Press, Boca Raton, FL, 1987).

    Google Scholar 

  3. Ponchel, G. & Duchêne, D. in High Performance Biomaterials (ed. Szycher, M.) 231–242 (Technomic, Lancaster, PA, 1991).

    Google Scholar 

  4. Davis, S. S. & Illum, L. Biomaterials 9, 111–115 (1988).

    Article  CAS  Google Scholar 

  5. Frisbie, C. D., Lawrence, F., Rozsnyai, A. N., Wrighton, M. S. & Charles, M. L. Science 265, 2071–2073 (1994).

    Article  ADS  CAS  Google Scholar 

  6. Langer, R. & Chasin, M. Biodegradable Polymers as Drug Delivery Systems (Marcel Decker, New York, 1990).

    Google Scholar 

  7. Chickering, D. E., Jacob, J. S. & Mathiowitz, E. React. Polym. 25, 189–206 (1995).

    Article  CAS  Google Scholar 

  8. Mathiowitz, E., Jacob, J., Chickering, D. & Pekarek, K. Macromolecules 26, 6756–6765 (1993).

    Article  ADS  CAS  Google Scholar 

  9. Chickering, D. E. & Mathiowitz, E. J. Control. Release 34, 251–261 (1995).

    Article  CAS  Google Scholar 

  10. Jacob, J., Santos, C., Carino, G., Chickering, D. & Mathiowitz, E. Proc. 22nd Int. Symp. Controlled Release of Bioactive Materials, 312–313 (Controlled Release Society, Inc., Deerfield, IL, 1995).

    Google Scholar 

  11. Chickering, D. E. III, Jacob, J. S. & Mathiowitz, E. Biotechnol. Bioeng. 52, 96–101 (1996).

    Article  CAS  Google Scholar 

  12. Carino, G., Santos, C., Chen, C. J. & Mathiowitz, E. Proc. 22nd Int. Symp. Controlled Release of Bioactive Materials, 314–315 (Controlled Release Society, Inc., Deerfield, IL, 1995).

    Google Scholar 

  13. Sanders, E. & Ashworth, C. T. Exp. Cell Res. 22, 137–145 (1961).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  15. Florence, A. & Jani, P. U. Drug Safety 10, 233–266 (1994).

    Article  CAS  Google Scholar 

  16. Florence, A. T., Hillery, A. M., Hussain, N. & Jani, P. U. J. Control. Release 36, 39–46 (1995).

    Article  CAS  Google Scholar 

  17. LeFevre, M. E., Olivo, R., Vanderhoff, J. W. & Joel, D. D. Proc. Soc. Exp. Biol. Med. 159, 298–302 (1978).

    Article  CAS  Google Scholar 

  18. Lefevre, M. E., Joel, D. D. & Schidlovsky, G. Proc. Soc. Exp. Biol. Med. 179, 522–528 (1985).

    Article  CAS  Google Scholar 

  19. Jani, P., Halbert, G. W., Langridge, J. & Florence, A. T. J. Pharm. Pharmacol. 41, 809–812 (1989).

    Article  CAS  Google Scholar 

  20. Jani, P., Halbert, G. W., Langridge, J. & Florence, A. T. J. Pharm. Pharmacol. 42, 821–826 (1990).

    Article  CAS  Google Scholar 

  21. Hillery, A. M., Jani, P. U. & Florence, A. T. J. Drug Target. 2, 151–156 (1994).

    Article  CAS  Google Scholar 

  22. Bockman, D. E. & Cooper, M. D. Am. J. Anat. 136, 455–478 (1973).

    Article  CAS  Google Scholar 

  23. Akers, M. J., Lach, J. L. & Fischer, L. J. J. Pharma. Sci. 62, 391–395 (1973).

    Article  CAS  Google Scholar 

  24. Goodman, L. S. & Gilman, A. The Pharmacological Basis of Therapeutics (Macmillan, New York, 1975).

    Google Scholar 

  25. Tutwiler, G. F., Kirsch, T. & Bridi, G. Diabetes 27, 856–867 (1978).

    Article  CAS  Google Scholar 

  26. Wolff, J. A. et al. Biotechniques 11, 474–485 (1991).

    CAS  PubMed  Google Scholar 

  27. Lau, C. et al. Hum. Gene Ther. 6, 1145–1151 (1995).

    Article  CAS  Google Scholar 

  28. Domb, A., Mathiowitz, E., Ron, E., Giannos, S. & Langer, R. J. Polym. Sci. 29, 571–579 (1991).

    Article  CAS  Google Scholar 

  29. Wolff, J. A. et al. Science 247, 1465–1468 (1990).

    Article  ADS  CAS  Google Scholar 

  30. Lee, S. W., Trapnell, B. C., Rade, J. J., Virmani, R. & Dichek, D. A. Circ. Res. 73, 797–807 (1993).

    Article  CAS  Google Scholar 

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Author notes

  1. Donald E. Chickering

    Present address: Sulzer Carbomedics, Austin, TX, 78752, USA

  2. Pravin Chaturvedi

    Present address: Vertex Pharmaceuticals, Cambridge, MA, USA

Authors and Affiliations

  1. Department of Molecular Pharmacology, Physiology and Biotechnology, Division of Biology and Medicine, Brown University, Providence, Rhode Island, 02912, USA

    Edith Mathiowitz, Jules S. Jacob, Yong S. Jong, Gerardo P. Carino, Camilla A. Santos, Kavita Vijayaraghavan, Sean Montgomery, Michael Bassett & Craig Morrell

  2. Sulzer Carbomedics, Austin, TX, 78752, USA

    Pravin Chaturvedi

Authors
  1. Edith Mathiowitz
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  2. Jules S. Jacob
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  4. Gerardo P. Carino
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  5. Donald E. Chickering
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  6. Pravin Chaturvedi
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  7. Camilla A. Santos
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  8. Kavita Vijayaraghavan
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  9. Sean Montgomery
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  10. Michael Bassett
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  11. Craig Morrell
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Mathiowitz, E., Jacob, J., Jong, Y. et al. Biologically erodable microspheres as potential oral drug delivery systems. Nature 386, 410–414 (1997). https://doi.org/10.1038/386410a0

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