Drug carriers are useful tools for controlling the
in vivo disposition of drugs. The distribution of carriers are determined by their tissue interaction depending on the anatomical and physiological characteristics of each tissue and the physicochemical and biological properties of carriers. Once these properties of carriers are quantitatively correlated with their tissue distribution, a proper drug carrier can be rationally developed. However, this is not the case for carriers which interact with blood components, such as blood cells and plasma proteins, before reaching to their targets. The properties of carriers will be altered by such interactions, which leads to various changes of the biofates of carriers. Carriers interact with plasma proteins in different ways : nonspecific interaction (adsorption), recognition by immune proteins, and metabolism and exchange of lipids. In general, the more plasma proteins bind to carriers, the faster they are eliminated from the blood circulation. Positively-charged carriers like cationic liposomes interact with negatively-charged plasma proteins, which sometimes leads to the aggregation of carriers and the embolization of blood vessels after intravascular administration. When drug carriers are recognized as non-self, they are removed by the mononuclear phagocyte system(MPS). The binding of immunoglobulins and complements to carriers extremely facilitates their removal by MPS. Mannan binding protein, an immune protein which recognize mannose or N-acetylglucosamine residue on virus infected cells, can interact with carriers possessing mannose moieties. In addition, binding of apolipoproteins triggers the metabolism of o/w emulsions followed by their uptake by hepatocytes
via apolipoprotein E-specific receptors. To regulate
in vivo distribution of drug carriers, therefore, their interactions with plasma proteins should be suppressed. Coating of carriers with hydrophilic macromolecules, such as poly(ethylene glycol) and ganglioside G
M1, is a promising approach to suppress such interactions. In conclusion, we can theoretically develop a well-designed drug carrier system by considering its interactions with blood components as well as with tissues.
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