Nanoparticles for the Delivery of Peptides and Proteins

  • P. Couvreur
  • F. Puisieux
Part of the NATO ASI Series book series (NSSA, volume 273)


Peptides drugs are gaining more and more interest as their role in physiopathology is better understood, and because of the progress in biotechnology and in conventional chemical synthesis as well. The development of DNA-recombination techniques have made these compounds available on a larger scale than in the past. However, the use of peptides in medicine is partly limited due to their easy degradation by proteolytic enzymes in the gastrointestinal tract, and therefore they have to be administered by injection. In addition, peptides are generally characterized by a short biological half-life, so that repeated injections are generally needed. Even after subcutaneous or intramuscular administration, a low bioavailability is often observed. Finally, most peptides pass poorly through biological barriers, due to their partition coefficient, which is unfavorable to lipidic structures. The foregoing considerations have led to the development of many new drug delivery systems. Among them, micro- and nanoparticles have been proposed for the safe and controlled administration of peptides and proteins. The main advantage of these microdispersed polymeric systems is their easy administration by a single injection whereas dosage forms larger in size may require a surgical incision. On the other hand, the difficulty of their removal from the injection site and their potential for catastrophic release (e.g. dose dumping) have also to be considered. Microparticulate systems may be convenient for other routes of administration (nasal, oral, buccal...). Furthermore, the large diversity of the synthetic and natural polymers available for micro- and nanoparticle preparation allows them to be considered as very flexible. Finally, in spite of their complexity and the possibility of down-regulation of receptors on continued dosing, these systems are of particular interest since they seem able to control the release rate and profile of numerous peptides and proteins and to improve their poor delivery characteristics as well.


Oral Delivery Peptide Drug Growth Hormone Release Factor Glycidyl Ester Associate Lymphoid Tissue 
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  1. Al Khouri, N., Roblot-Treupel, L., Fessi, H, Devissaguet, J.P. and Puisieux, F., 1986. Development of a new process for the manufacture of polyisobutylcyanoacrylate nanocapsules, Int.J.Pharm., 28:125.CrossRefGoogle Scholar
  2. Aprahamian, M., Michel, C., Humbert, W., Devissaguet, J.P. and Damgé, C., 1987. Transmucosal passage of polyalkylcyanoacrylate nanocapsules as a new drug carrier in the small intestine, Biol.of the Cell, 61:69.CrossRefGoogle Scholar
  3. Artursson, P., Edman, P., Laakso, T. and Sjöholm, I., 1984. Characterization of polyacryl starch microparticles as carriers for proteins and drugs, J.Pharm.Sci., 73:1507.PubMedCrossRefGoogle Scholar
  4. Artursson, P., Edman, P. and Sjöholm, I., 1984. Duration of action of dextranase entrapped in polyacrylstarch microparticles in vivo, J.Pharm.Exp.Ther., 231:705.Google Scholar
  5. Couvreur, P., Grislain, L., Lenaerts, V., Brasseur, F., Guiot, P. and Biernacki, A., 1986, Biodegradable polymeric nanoparticles as drug carrier for antitumor agents, in: Polymeric Nanoparticles and Microspheres, P. Guiot and P. Couvreur, eds., CRC Press, Boca Raton.Google Scholar
  6. Couvreur, P., Roland, M. and Speiser, P., 1982, Biodegradable particles containing a biologically active substance. US Patent n° 4, 329, 332.Google Scholar
  7. Couvreur, P., Lenaerts, V., Kante, B., Roland, M. and Speiser, P., 1980. Oral and parenteral administration of insulin associated to hydrolysable nanoparticles, Acta Pharm. Technol., 26:220.Google Scholar
  8. Damgé, C., Michel, C., Aprahamian, M. and Couvreur, P., 1988. New approach for oral administration of insulin with polyalkylcyanoacrylate nanacapsules as drug carrier, Diabetes, 37:246.PubMedCrossRefGoogle Scholar
  9. Damgé, C., Michel, C., Aprahanian, M., and Couvreur, P., 1991, Personal Communication.Google Scholar
  10. Damgé, C., Michel, C., Aprahanian, M., Couvreur, P. and Devissaguet, J.P., 1990. Nanocapsules as carriers for oral peptide delivery, J.Control.Rel., 13:233.CrossRefGoogle Scholar
  11. Edman, P. Artursson, P., Björk, E. and Davidsson, B., 1987. Immobilized L-asparaginase-L-glutaminase from Acinetobacter glutaminasificans in microspheres: some properties in vivo and in an extracorporeal system, Int.J.Pharm., 34:225.CrossRefGoogle Scholar
  12. Eldridge, J.H., Hammond, C.J., Meulbroek, J.A., Staas, J.K., Gilley, R.M. and Tice, T.R., 1990. Controlled vaccine release in the gut associated lymphoid tissue. I. Orally administered biodegradable microspheres target the Peyer’s patches, J.Control.Rel., 11:205.CrossRefGoogle Scholar
  13. Le Fèvre, M.E., Joël, D.D. and Shidlovsky, G., 1985. Retention of ingested latex particles in Peyer’s patches of germfree and conventional mice, Proc.Soc.Exp.Biol.Med., 179:522.CrossRefGoogle Scholar
  14. Le Fèvre, M.E., Warren, J.B. and Joël, D.D., 1985. Particles and macrophages in murine Peyer’s patches, Expl.Cell Biol., 53:121.Google Scholar
  15. Gautier, J.C., Grangier, J.L., Barbier, A., Dupont, P., Dussossoy, D., Pastor, G. and Couvreur, P., 1992. Biodegradable nanoparticles for subcutaneous administration of growth hormone releasing factor (hGRF), J.Control.Rel., 20:67.CrossRefGoogle Scholar
  16. Gilligan, C.A. and Li Wan Po, A., 1991. Oral vaccines: design and delivery, Int.J.Pharm., 75:1.CrossRefGoogle Scholar
  17. Grangier, J.L., Puygrenier, M., Gautier, J.C. and Couvreur, P., 1991. Nanoparticles as carriers for growth hormone releasing factors (GRF), J.Control.Rel., 15:3.CrossRefGoogle Scholar
  18. Grislain, L., Couvreur, P., Lenaerts, V., Roland, M., Deprez-Decampeneere, D. and Speiser, P., 1983. Pharmacokinetics and distribution of biodegradable drug-carrier, IntJ.Pharm., 15:335.CrossRefGoogle Scholar
  19. Jani, P., Halbert, G.W., Langridge, J. and Florence, A.T., 1989. The uptake and translocation of latex nanospheres and microspheres after oral administration to rats, J.Pharm.Pharmacol., 41:809.PubMedCrossRefGoogle Scholar
  20. Jani, P., Halbert, G.W., Langridge, J. and Florence, A.T., 1990. Nanoparticle uptake by the rat gastrointestinal mucosa: quantitation and particle size dependency, J.Pharm.Pharmacol., 42:821.PubMedCrossRefGoogle Scholar
  21. Kroehenbuhl, J.P. and Neutra, M.R., 1992, Molecular and cellular basis of immune protection of mucosal surfaces, Physiol.Rev., in press.Google Scholar
  22. Lenaerts, V., Couvreur, P., Christiaens-Leyh, D., Joiris, E., Roland, M., Rollman, B. and Speiser, P., 1984. Degradation of poly(isobutylcyanoacrylate) nanoparticles, Biomaterials, 5:65.PubMedCrossRefGoogle Scholar
  23. Maincent, P., Le Verge, R., Sado, P.A., Couvreur, P. and Devissaguet, J.P., 1986. Disposition kinetics and oral bioavailability of vincamine-loaded polyalkylcyanoacrylate nanoparticles, J.Pharm.Sci., 75:955.PubMedCrossRefGoogle Scholar
  24. Michel, C., Aprahamian, M., Defontaine, L., Couvreur, P. and Damgé, C., 1991. The effect of site of administration in the gastrointestinal tract on the absorption of insulin from nanocapsules in diabetic rats, J.Pharm.Pharmacol., 43:1.PubMedCrossRefGoogle Scholar
  25. Michel, C., Couvreur, P., Vranckx, M., Damgé, C., Puisieux, F. and Balschmidt, P., 1990, Compositions pharmaceutiques contenant de l’insuline pour utilisation dans le traitement du diabète et procédé de préparation de telles compositions pharmaceutiques. Demande de Brevet Belge.Google Scholar
  26. Morishita, M., Morishita, I., Takayama, K., Machida, Y. and Nagai, T., 1992. Novel oral microspheres of insulin with protease inhibitor protecting from enzymatic degradation, Int.J.Pharm., 78:1.CrossRefGoogle Scholar
  27. Morishita, I., Morishita, M., Takayama, K., Machida, Y. and Nagai, T., 1992. Hypoglycemic effect of novel oral microspheres of insulin with protease inhibitor in normal and diabetic rats, Int.J.Pharm., 78:9.CrossRefGoogle Scholar
  28. O’Hagan, D.T., 1990. Intestinal translocation of particulates-implications of drug and antigen delivery, Adv.Drug Deliv.Rev., 5:265.CrossRefGoogle Scholar
  29. O’Hagan, D.T., Palin, K. and Davis, S.S., 1989. Poly(butyl-2-cyanoacrylate particles as adjuvant for oral immunization, Vaccine, 7:213.PubMedCrossRefGoogle Scholar
  30. O’Hagan, D.T., Palin, K., Davis, S.S., Artursson, P. and Sjoholm, I., 1989. Microparticles as potentially orally active immunological adjuvants, Vaccine, 7:421.PubMedCrossRefGoogle Scholar
  31. Pappo, J., Ermak, T.H. and Steger, H.J., 1991. Monoclonal antibody-directed targeting of fluorescent polystyrene microspheres to Peyer’s patch M cells, Immunology, 73:277.PubMedGoogle Scholar
  32. Sanders, E. and Ashworth, C.T., 1961. A study of paniculate intestinal absorption and hepatocellular uptake, Exp.Cell.Res., 22:137.PubMedCrossRefGoogle Scholar
  33. Verdun, C., Brasseur, F., Vranckx, H., Couvreur, P. and Roland, M., 1990. Tissue distribution of doxorubicin associated with polyisohexylcyanoacrylate nanoparticles, Cancer Chemother.Pharmacol., 26:13.PubMedCrossRefGoogle Scholar
  34. Volkheimer, G., 1983. Hoematogenous dissemiation of ingested Polyvinylchloride particles, Ann.N.Y.Acad.Sci., 409:164.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1994

Authors and Affiliations

  • P. Couvreur
    • 1
  • F. Puisieux
    • 1
  1. 1.Laboratoire de Pharmacie Galénique, URA CNRS 1218Université Paris XIChatenay-Malabry CedexFrance

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