Nanoparticles opsonization

Particles introduced into the bloodstream are covered rapidly by components of the circulation, such as plasma proteins, in a process called opsonization. Opsonization makes the particles recognizable to the body s major defense system, the reticuloendothelial system (RES). The RES comprises a diffuse system of phagocytic cells (which engulf inert material) that are primarily associated with the connective tissues in the liver, spleen, and lymph nodes. Macrophage (Kupffer) cells in the liver and macrophages of the spleen and circulation are important in removing particles identified by opsonization. A significant fraction of nanoparticles can be cleared from the circulation system in as little as 15 minutes [48, 49],... 

Moghimi, S. M., and Szebeni, J. (2003), Stealth liposomes and long circulating nanoparticles Critical issues in pharmacokinetics, opsonization and protein-binding properties, Prog. Lipid Res., 42(6), 463-478. 

Amellar, T. Marsaud, V. Legraand, P. Gref, R. Barratt, G. Renoir, J.M. Polyester-poly(ethylene glycol) nanoparticles loaded with the pure antiestrogen RU 58668 physicochemical and opsonization properties. Pharm. Res. 2003, 20 (7), 1063-1070 (and references therein). 

Two pivotal discoveries enabled the full potential of Upo-somes to be realized. The first was the discovery in the late 1980s and early 1990s that the presence of additional molecnles snch as poly(oxyethylene) bonded onto the liposome snrface decreased their clearance by partially preventing liver and spleen nptake of i.v. injected liposomes. These are now often referred to as stealth liposomes as this effect enables them to escape recognition by the liver and spleen with the beneht of long drcnlation times. This observation was made almost in parallel with the discovery that polystyrene nanoparticles coated with a poly(oxyethylene) polymer also showed rednced liver and spleen nptake. It is likely that a reduction in the coating of these liposomes by plasma proteins (opsonization), and their rednced aggregation in the blood are responsible for the increased circnlation time of... 

Owens III D E, Peppas N A. Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int. J. Pharm. In Press, Corrected Proof. 

Ibrahim, M.A., Ismail, A., Fetouh, M.I., Gopferich, A. Stability of insulin during the erosion of polyflactic acid) and poly(lactic-co-glycolic acid) microspheres. J. Contr. Release, 106, 241, 2005. Owens, D.E., Peppas, N.A. Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int. J. Pharm., 307, 93, 2006. 

In spite of all the advantages, cationic nanoparticles have some challenges. Some major drawbacks of these systems include instability, risk of aggregation, toxicity, opsonization and clearance by the mononuclear phagocyte system (MPS). To overcome these problems, cationic nanoparticles should be as small and neutral as possible and nanoparticles can be coated with PEG. PEG can provide a hydrophilic surface to nanocarriers and also a cationic surface charge and prevent opsonization. In this way, PEG-coated nanoparticles have a prolonged circulation life and protect photolytic degradation. 

---