Solid Lipid Nanoparticles (SLN) are a biodegradable drug carrier system with the potential to be introduced to the clinic. Surface-modified SLN were produced and optimized using the hydrophilic block copolymers poloxamine 908 and poloxamer 407 as stabilizing agents. These two block copolymers are known to modify the organ distribution of colloidal non-iodegradable model carriers administered via the i.v. route when adsorbed on their surface (i.e. avoidance of Mononuclear Phagocytic System (MPS) recognition, i.e. liver/spleen uptake). The interactions of surface-modified SLN with blood proteins were studied by two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). The resulting protein adsorption patterns proved that all surface-modified SLN formulations showed an extraordinary low degree of interaction with the plasma proteins. A preferential adsorption of albumin, fibrinogen and apolipoproteins A-I, A-IV and C-III was detected The presence of apolipoproteins A-I and A-IV is discussed as being responsible for a modulating effect on the organ distribution. From this data obtained up to now surface-modified SLN might be a biodegradable colloidal carrier system efficient in avoiding the MPS recognition.