Reticuloendothelial recognition

There may be biological sensitivities to the conformational presentation and sizing of the lipid formulation. For example the ability of antibodies to distinguish between lamellar organizing lipids and hexagonal-phase lipids are known and may form the basis for certain types of autoimmune dysfunction. Biological factors such as reticuloendothelial cell recognition of particles provide further impetus for control of the particle size and stability. 

In 1986, Muromonab CD-3 (OKT-3), which is a monoclonal antibody was first introduced to clinical practice, and the agent has been effective in reversing corticosteroid-resistant acute rejection in renal, liver, and cardiac transplant recipients. OKT-3 is administered only by intravenous injection and has a harmonic half-life of approximately 18 h. It binds specifically to the CD-3 complex, which is involved in antigen recognition and cell stimulation, on the surface of T lymphocytes. Immediately after administration, CD-3-positive T lymphocytes are abruptly removed from the circulation. OKT-3 may be removed by opsonization by the reticuloendothelial system when bound to T lymphocytes, or by human antimurine antibody production [230]. 

The main problem to be overcome is their removal by phagocytic cells (macrophages) of the reticuloendothelial system (RES) and in particular the Kupffer cells of the liver. The main target of any research on nano-partides is to modify the surface of the particles in such a way to avoid RES recognition. 

Generally, the amphiphilic core/shell stmcture of polymeric micelles is formed from block polymers. Polyethylene glycol (PEG) and polyethylene oxide (PEO) are often used as the hydrophilic blocks. They have been shotvn to prevent recognition by the reticuloendothelial system and increase circulation time in vivo. As in the case of liposomes and niosomes, the grafting of specific ligand molecules on the surface of the polymeric micelles allows... 

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