title: Covalent attachment of apolipoprotein A-I and apolipoprotein B-100 to albumin nanoparticles enables drug transport into the brain.
abstract: Apolipoprotein E3, A-I as well as B-100 were covalently attached to human serum albumin nanoparticles via the NHS-PEG-Mal 3400 linker. Loperamide as a model drug was bound to these nanoparticles, and the antinociceptive reaction of these preparations was recorded after intravenous injection in mice by the tail-flick test. After 15 min, all three nanoparticle preparations with the coupled apolipoproteins E3, A-I, and B-100 yielded considerable antinociceptive effects, which lasted over 1 h. The maximally possible effects [MPE] of these preparations amounted to 95%, 65%, and 50%, respectively, and were statistically different from the controls (p<0.02), whereas the loperamide solution achieved no effect. This result demonstrates that more than one mechanism is involved in the interaction of nanoparticles with the brain endothelial cells and the resulting delivery of drugs to the central nervous system.
authors.affiliation: Institut für Pharmazeutische Technologie, Biozentrum, Johann Wolfgang Goethe-Universität Frankfurt, Germany. Kreuter@em.uni-frankfurt.de
authors.forename: Jörg
authors.initials: J
authors.lastname: Kreuter
authors.forename: Telli
authors.initials: T
authors.lastname: Hekmatara
authors.forename: Sebastian
authors.initials: S
authors.lastname: Dreis
authors.forename: Tikva
authors.initials: T
authors.lastname: Vogel
authors.forename: Svetlana
authors.initials: S
authors.lastname: Gelperina
authors.forename: Klaus
authors.initials: K
authors.lastname: Langer
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000737:chemistry / Q000493:pharmacokinetics*; D053299:Apolipoprotein B-100 / Q000737:chemistry / Q000493:pharmacokinetics*; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D008139:Loperamide / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D053758:Nanoparticles / Q000737:chemistry*; D010146:Pain / Q000188:drug therapy; D010147:Pain Measurement / Q000187:drug effects; D010316:Particle Size
chemical_list: D016632:Apolipoprotein A-I; D053299:Apolipoprotein B-100; D004337:Drug Carriers; D008139:Loperamide