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 influenced by the interaction with plasma proteins after i.v. administration. Serum protein adsorption on lipid drug conjugate nanoparticles, a new carrier system for i.v. application, was investigated by 2-dimensional electrophoresis (2-DE). The particles were surface-modified to target them to the brain. To assess the protein adsorption pattern after i.v. injection in mice prior to in vivo studies, the particles were incubated in mouse serum. Incubation in human serum was carried out in parallel to investigate similarities or differences in the protein patterns obtained from men and mice. Distinct differences were found. Particles incubated in human serum showed preferential adsorption of apolipoproteins A-I, A-IV and E. Previously, preferential adsorption of ApoE was reported as one important factor for targeting 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 localization of the LDC nanoparticles at the blood-brain barrier and diffusion of the marker Nile Red into the brain could be shown by confocal laser-scanning microscopy. Differences of the obtained adsorption patterns are discussed with regard to their relevance for correlations of in vitro and in vivo data obtained from different species.
Department of Pharmaceutics, Biopharmaceutics and Biotechnologie, Free University of Berlin, Kelchstr. 31, D-12169 Berlin, Germany.
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A
Gessner
C
C
Olbrich
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W
Schröder
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O
Kayser
R H
RH
Müller
D000327:Adsorption; D000818:Animals; D016632:Apolipoprotein A-I / Q000008:administration & dosage; D001054:Apolipoproteins A / Q000008:administration & dosage; D001057:Apolipoproteins E / Q000008:administration & dosage; D001798:Blood Proteins / Q000378:metabolism*; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D016503:Drug Delivery Systems; D006801:Humans; D051379:Mice; D013045:Species Specificity
D016632:Apolipoprotein A-I; D001054:Apolipoproteins A; D001057:Apolipoproteins E; D001798:Blood Proteins; C022205:apolipoprotein A-IV