title: Renal Targeting: Peptide-Based Drug Delivery to Proximal Tubule Cells.
abstract: Kidney-specific drug targeting is an attractive strategy to reduce unwanted side effects and to enhance drug efficacy within the renal tissue. For this purpose a novel kidney-specific drug carrier was developed. The peptide sequence (KKEEE)3K triggers exceptional renal specificity at high accumulation rates. Micro-PET imaging studies of megalin-deficient mice indicate that the cellular endocytosis of this carrier is mediated by megalin. This assumption is supported by immunohistochemical analysis of FITC-labeled carrier peptide, which exclusively accumulated at the apical side of proximal tubule cells within the renal cortex. Scintigraphic studies of modified ciprofloxacin conjugated to (KKEEE)3K confirmed the excellent drug targeting potential of the peptide carrier. The conjugate accumulated entirely in the kidneys, revealing flawless redirection of ciprofloxacin, a compound that is mainly excreted by the liver. In conclusion, these results suggest the potential of (KKEEE)3K as a promising candidate for kidney-targeted drug delivery to proximal tubule cells.
authors.affiliation: Department of Nuclear Medicine, Heidelberg University Hospital , INF 400, 69120 Heidelberg, Germany.
authors.forename: Artjom
authors.initials: A
authors.lastname: Wischnjow
authors.affiliation: Department of Nuclear Medicine, Heidelberg University Hospital , INF 400, 69120 Heidelberg, Germany.
authors.forename: Dikran
authors.initials: D
authors.lastname: Sarko
authors.affiliation: Department of Nuclear Medicine, Heidelberg University Hospital , INF 400, 69120 Heidelberg, Germany.|Merck KGaA , Frankfurter Strasse 250, 64293 Darmstadt, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Janzer
authors.affiliation: Department of Nuclear Medicine, Heidelberg University Hospital , INF 400, 69120 Heidelberg, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Kaufman
authors.affiliation: Department of Nuclear Medicine, Heidelberg University Hospital , INF 400, 69120 Heidelberg, Germany.
authors.forename: Barbro
authors.initials: B
authors.lastname: Beijer
authors.affiliation: Department of Nuclear Medicine, Heidelberg University Hospital , INF 400, 69120 Heidelberg, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Brings
authors.affiliation: Department of Nuclear Medicine, Heidelberg University Hospital , INF 400, 69120 Heidelberg, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Haberkorn
authors.affiliation: Merck KGaA , Frankfurter Strasse 250, 64293 Darmstadt, Germany.
authors.forename: Gregor
authors.initials: G
authors.lastname: Larbig
authors.affiliation: Merck KGaA , Frankfurter Strasse 250, 64293 Darmstadt, Germany.
authors.forename: Armin
authors.initials: A
authors.lastname: Kübelbeck
authors.affiliation: Department of Nuclear Medicine, Heidelberg University Hospital , INF 400, 69120 Heidelberg, Germany.
authors.forename: Walter
authors.initials: W
authors.lastname: Mier
mesh_terms: D000368:Aged; D000818:Animals; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000187:drug effects*; D051379:Mice; D010455:Peptides / Q000008:administration & dosage*; D049268:Positron-Emission Tomography
chemical_list: D010455:Peptides