Development of a New Class of Nanoparticles which Avoid Phagocytosis by Inhibiting Complement Activation
The development of colloidal systems (liposomes, nanoparticles) as efficient drug carriers is limited by their distribution within the organism. It is now well established that after intravenous administration these particles are rapidly opsonized by plasma proteins. These adsorbed proteins promote recognition and uptake by cells of the mononuclear phagocyte system (MPS), particularly the Küpffer cells of the liver, but also spleen and bone-marrow macrophages (Puisieux et al., 1994). Activation of complement, especially by the alternative pathway, plays an important role in the processes of opsonization and phagocytosis. If colloidal drug carrier systems are to remain in the blood compartment for any length of time and deliver their contents to organs other than the MPS, strategies for avoiding opsonization must be developed.
KeywordsComplement Activation Alternative Pathway Complement Cascade Mononuclear Phagocyte System Sulfated Glucosamine
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- Couvreur, P., Grislain, L., Lenaerts, V., Brasseur, F., Guiot, P., and Biornacki, A., 1986, Biodegradable polymeric nanoparticles as drug carriers for antitumor agents, in: Polymeric Nanoparticles and Microspheres, P. Guiot and P. Couvreur, eds., CRC Press, Boca Raton.Google Scholar
- Ekre, H.P., Naparstek, Y., Lider, O., Hydén, P., Hägermark, Ö, Nilsson, T., Vlodavsky, I. and Cohen, I., 1992, Anti-inflammatory effects of heparin and its derivatives inhibition of complement and of lymphocyte migration, in: Heparin and Related Polysaccharides. D.A. Lane, ed., Plenum Press, New York.Google Scholar
- Huve P., 1994, Comprendre et éviter la capture des nanoparticules de poly (acide-lactique) par le système des phagocytes mononucléaires, Ph.D. Thesis, Université Paris-Sud, Sci. Pharm.Google Scholar
- Mayer, M.M., 1961, Complement and complement fixation, in: Experimental Immunochemistry, EA. Kabat and M.M. Mayer, eds., 2nd Edn, Thomas, Springfield.Google Scholar
- Puisieux, F., Barratt, G., Couarraze, G., Couvreur, P., Devisssaguet, J.P., Dubernet, C, Fattal, E., Fessi, H., Vauthier, C. and Benita, S., 1994, Polymeric micro-and nanoparticles as drug carriers, in: Polymeric Biomaterials, S. Dumitriu, ed., M. Dekker, New York.Google Scholar
- Riesenfeld, J, Olsson, P., Sanchez, J. and Molines, E. Surface modification with functionally active heparin. Med. Dev. Tech. March 1995:24.Google Scholar