Non-phagocytic uptake of intravenously injected microspheres in rat spleen: influence of particle size and hydrophilic coating.

A recent development in prolonging the circulation time of drug carriers, such as liposomes and microspheres, has been to minimize their removal by macrophages of the reticuloendothelial system by covering their surface with hydrophilic polymers such as poloxamers, poloxamines and poly(ethyleneglycols). Here we demonstrate that this strategy may not necessarily prolong the circulatory half-life of drug carriers in all animal models. In rats, as opposed to rabbits, a non-phagocytic mechanism in the spleen may be triggered to remove efficiently from the blood drug carriers coated with hydrophilic coatings. Both the size of particle and its hydrophilic coating may act synergistically to trigger this non-phagocytic mechanism. In rats, a remarkable log to log relationship between particle size and spleen uptake was observed for both uncoated and polymeric coated microspheres. The potential implication of these observations in site-specific delivery of drug carriers is discussed.