The role of plasma proteins in brain targeting: species dependent protein adsorption patterns on brain-specific lipid drug conjugate (LDC) nanoparticles

The in vivo organ distribution of particulate drug carriers is decisively i nfluenced by the interaction with plasma proteins after i.v. administration . Serum protein adsorption on lipid drug conjugate nanoparticles. a new car rier system for i.v. application. was investigated by 2-dimensional electro phoresis (2-DE). The particles were surface-modified to target them to the brain. To assess the protein adsorption pattern after i.v. injection in mic e prior to in vivo studies. the particles were incubated in mouse serum. In cubation in human serum was carried out in parallel to investigate similari ties or differences in the protein patterns obtained from men and mice. Dis tinct differences were found, particles incubated in human serum showed pre ferential adsorption of apolipoproteins A-I, A-IV and E. Previously. prefer ential adsorption of ApoE was reported as one important factor for targetin g of Tween(R) 80 modified polybutylcyanoacrylate nanoparticles to the brain . Preferential adsorption of ApoA-I and A-IV took place after incubation in mouse serum, adsorption of ApoE could not be clearly confirmed. In vivo lo calization of the LDC nanoparticles at the blood-brain barrier and diffusio n of the marker Nile Red into the brain could be shown by confocal laser-sc anning microscopy. Differences of the obtained adsorption patterns are disc ussed with regard to their relevance for correlations of in vitro and in vi vo data obtained from different species. (C) 2001 Elsevier Science B.V. All rights reserved.