title: Polysorbate-stabilized solid lipid nanoparticles as colloidal carriers for intravenous targeting of drugs to the brain: comparison of plasma protein adsorption patterns.
abstract: Plasma proteins enriched on the surface of drug-delivery-purpose nanoparticles are regarded as key factors for determination of in vivo organ distribution after intravenous injection. Polysorbate 80-coated polybutylcyanoacrylate (PBCA) nanoparticles, preferentially adsorbing apolipoprotein E (apoE) on their surface, have previously been considered to deliver various drugs to the brain. In the present study, in vivo well tolerable solid lipid nanoparticles (SLN) using different types of polysorbates as stabilizers were produced. The influence of the different surfactants on in vitro adsorption of human plasma proteins was investigated using two-dimensional polyacrylamide gel electrophoresis (2-DE). Possible correlations of different amounts of adsorbed apoE to the hydrophilic-lipophilic balance (HLB) of the polysorbates are shown and discussed. Apolipoprotein C-II, albumin and immunoglobulin G, which are also decisive plasma proteins with regard to site-specific drug delivery of intravenously injected carriers to the brain, are compared with regard to adsorption. Moreover, certain similarities to the plasma protein adsorption patterns of previously analysed brain-specific PBCA nanoparticles could be detected. Despite some differences in adsorption behavior of proteins on the surface of polysorbate-stabilized SLN and PBCA nanoparticles, we conclude that in both cases polysorbate 80 might have the highest potential to deliver drugs to the brain.
authors.affiliation: Department of Pharmaceutics, Biopharmaceutics and Quality Management, Institute of Pharmacy, The Free University of Berlin, Berlin, Germany.
authors.forename: Torsten M
authors.initials: TM
authors.lastname: Göppert
authors.forename: Rainer H
authors.initials: RH
authors.lastname: Müller
mesh_terms: D000327:Adsorption; D001057:Apolipoproteins E / Q000008:administration & dosage / Q000493:pharmacokinetics; D001798:Blood Proteins / Q000378:metabolism*; D001921:Brain / Q000187:drug effects*; D003102:Colloids; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D004591:Electrophoresis, Polyacrylamide Gel; D004659:Enbucrilate; D006801:Humans; D007202:Indicators and Reagents; D007275:Injections, Intravenous; D008055:Lipids / Q000737:chemistry*; D008863:Microspheres; D010316:Particle Size; D011136:Polysorbates / Q000737:chemistry*; D011506:Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics; D013499:Surface Properties
chemical_list: D001057:Apolipoproteins E; D001798:Blood Proteins; D003102:Colloids; D004337:Drug Carriers; D007202:Indicators and Reagents; D008055:Lipids; D011136:Polysorbates; D011506:Proteins; D004659:Enbucrilate