Nanoparticles for the Delivery of Peptides and Proteins
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.
KeywordsOral Delivery Peptide Drug Growth Hormone Release Factor Glycidyl Ester Associate Lymphoid Tissue
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- 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
- 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
- Couvreur, P., Roland, M. and Speiser, P., 1982, Biodegradable particles containing a biologically active substance. US Patent n° 4, 329, 332.Google Scholar
- 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
- Damgé, C., Michel, C., Aprahanian, M., and Couvreur, P., 1991, Personal Communication.Google Scholar
- 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
- Kroehenbuhl, J.P. and Neutra, M.R., 1992, Molecular and cellular basis of immune protection of mucosal surfaces, Physiol.Rev., in press.Google Scholar
- 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