Arbeitskreis Prof. Dr. Gert Fricker
Prof. Dr. G. Fricker
Telefon: 54 - 83 36
Telefax: 54 - 59 71
E-Mail: Gert.Fricker@uni-hd.de
Arbeitsgebiete:
1. Arzneimitteltransport durch die Blut-Hirn Schranke:
Viele potentiell hochwirksame ZNS-aktive Wirkstoffe vermögen die Blut-Hirn Schranke nicht zu durchdringen, weil Sie aufgrund ihrer Polarität die Lipidbarriere der Gehirnkapillarendothelzellen nicht durchdringen und/oder weil sie nicht von aktiven Transportsystemen in den Endothelzellen erkannt und wieder in den Blutkreislauf zurück transportiert werden können.
Diese Transportsysteme werden auf molekularer Ebene identifiziert und ihre Funktion und Expression sowie ihre Rolle im Arzneimitteltransport werden untersucht. Besondere Aufmerksamkeit wird dabei dem p-Glycoprotein (ABCB1; mdr1-Genprodukt) und dem Breast Cancer Resistance Protein (ABCG2) gewidmet.
Die Transportproteine werden in primären Zellkulturen aus Gehirnkapillarendothelzellen, immortalisierten Zelllinien, isolierten und funktionell intakten Gehirnkapillaren sowie in vivo in Ratten untersucht.
Das Projekt ist Bestandteil einer internationalen Zusammenarbeit zwischen unserer Abteilung den National Institutes of Environmental Health Sciences (Research Triangle Park, NC, USA), der Tohoku University (Sendai, Japan), der Universität Wien (Österreich) und weiteren Partnern aus Hochschule und Industrie.
2. Drug Targeting
Entwicklung von kolloidalen Trägersystemen (Nanopartikel, Liposomen) mit denen nichtpermeable Wirkstoffe durch Kapillarendothelzellen ins Gehirn eingeschleust werden können. Diese Trägersysteme werden an zielsuchende Vektoren (z. B. Antikörper) gekoppelt, welche bestimmte Rezeptoren an der Blut-Hirn-Schranke erkennen und über diese Rezeptoren durch Transzytose durch das Kapillarendothel ins Gehirn eingeschleust.
Das Projekt wird in Zusammenarbeit mit Universität Basel (Schweiz) und der Universität Frankfurt und weiteren Partnern aus der Industrie durchgeführt.
3. Entwicklung vorhersagekräftiger in vitro-Modelle zur Untersuchung von Transportmechanismen
Molekulare Mechanismen des zellulären Transports lassen sich kaum in vivo untersuchen. Ziel des Projektes ist es deshalb, bestehende in vitro-Modelle im Hinblick auf ihren Vorhersagecharakter zu verbessern, bzw. neue Modelle zu etablieren.
Im Mittelpunkt der Untersuchungen stehen Modelle zur Prüfung intestinaler Resorptionsprozesse und Modelle von Kapillarendothelzellen zur Simulation der Blut-Hirn Schranke. Bei beiden Modellen ist die Ausbildung konfluenter und dichter Monolayer ein Schlüsselproblem für die Vorhersage der Wirkstoffpermeation in vivo. Es wird deshalb gezielt nach Faktoren gesucht, über welche sich Dichtigkeit und Polarität der Zellmonolayer beeinflussen lassen.
4. Verbesserung der Wirkstoffresorption aus dem Gastrointestinaltrakt
Schwerlösliche Wirkstoffe und Peptidarzneistoffe können oft nur schwer oral verabreicht werden, da sie im Gastrointestinaltrakt schnell abgebaut oder nur in sehr geringer Menge resorbiert werden. Es wird nach Möglichkeiten gesucht, die Löslichkeit und die Resorption solcher Wirkstoffe durch die Darmwand zu verbessern, ohne daß es dabei zu einer Schädigung der Darmmucosa kommt. Untersuchte Darreichungsformen sind Mikroemulsionssysteme sowie feste Lipidnanopartikelsysteme.
Das Projekt ist Bestandteil einer Kooperation mit der Universität Odense (Dänemark) der Universität Kaiserslautern sowie mehrerer Insutriepartner
5. Zelluläre Transportsysteme
In diesem Projekt werden Membrantransportsysteme für organische Anionen und Kationen in Blut-Hirn Schranke und im Choroid Plexus funktionell und auf molekularer Ebene untersucht. Es wird mit isolierten Membranfraktionen, isolierten Zellen und ganzen, funktionell intakten Gewebestücken geprüft, ob Membrantransporter, die physiologisch vorhandene organische Anionen oder Kationen transportieren, auch Affinität für bestimmte Pharmaka besitzen. Die in den in vitro-Modellen erhaltenen Ergebnisse werden mit pharmakokinetischen in vivo-Befunden korreliert.
Das Projekt ist eine Zusammenarbeit zwischen dem Institut, der Yale Medical School (New Haven, USA), einer Arbeitsgruppe am NIH/NIEHS, (Research Triangle Park, NC, USA) und industriellen Partnern.
Zusammenarbeiten:
D.S. Miller NIEH/NIEHS Research Triangle Park, NC, USA
T. Terasaki Tohoku University, Sendai, Japan
P.O. Couraud INSERM, Cochin Institute, Paris, Frankreich
M. Udenäs - Hammarlund Universität Uppsala, Uppsala, Schweden
M. Brandl Universität Odense, Odense, Dänemark
H. Potschka Ludwig Maximilians-Universität, München
J. Huwyler Universität Basel, Basel, Schweiz
Ausgewählte Veröffentlichungen
Lehrbuch:
Biopharmazie
P. Langguth, G. Fricker, H. Wunderli-Allenspach
VCH-Wiley, 2004
Mahringer A, Ardjomand-Woelkart K, Bauer R, Fricker G, Efferth T. Alkamides from Echinacea angustifolia Interact with P-Glycoprotein of Primary Brain Capillary Endothelial Cells Isolated from Porcine Brain Blood Vessels. Planta Med. 2013 Jan 15. [Epub ahead of print]
Zadeh-Khorasani M, Nolte T, Mueller TD, Pechlivanis M, Rueff F, Wollenberg A, Fricker G, Wolf E, Siebeck M, Gropp R. NOD-scid IL2R γnull mice engrafted with human peripheral blood mononuclear cells as a model to test therapeutics targeting human signaling pathways. J Transl Med. 2013 Jan 7;11:4.
Frank KJ, Westedt U, Rosenblatt KM, Hölig P, Rosenberg J, Mägerlein M, Fricker G, Brandl M.The amorphous solid dispersion of the poorly soluble ABT-102 forms nano/microparticulate structures in aqueous medium: impact on solubility. Int J Nanomedicine. 2012;7:5757-68.
Gerbeth K, Hüsch J, Fricker G, Werz O, Schubert-Zsilavecz M, Abdel-Tawab M. In vitro metabolism, permeation, and brain availability of six major boswellic acids from Boswellia serrata gum resins. Fitoterapia. 2013 Jan;84:99-106.
Hüsch J, Bohnet J, Fricker G, Skarke C, Artaria C, Appendino G, Schubert-Zsilavecz M, Abdel-Tawab M.Enhanced absorption of boswellic acids by a lecithin delivery form (Phytosome(®)) of Boswellia extract. Fitoterapia. 2013 Jan;84:89-98.
Fischer SM, Parmentier J, Buckley ST, Reimold I, Brandl M, Fricker G.Oral bioavailability of ketoprofen in suspension and solution formulations in rats: the influence of poloxamer 188.J Pharm Pharmacol. 2012 Nov;64(11):1631-7.
Martins S, Tho I, Reimold I, Fricker G, Souto E, Ferreira D, Brandl M.Brain delivery of camptothecin by means of solid lipid nanoparticles: formulation design, in vitro and in vivo studies. Int J Pharm. 2012 Dec 15;439(1-2):49-62
Hüsch J, Gerbeth K, Fricker G, Setzer C, Zirkel J, Rebmann H, Schubert-Zsilavecz M, Abdel-Tawab M.Effect of phospholipid-based formulations of Boswellia serrata extract on the solubility, permeability, and absorption of the individual boswellic acid constituents present.J Nat Prod. 2012 Oct 26;75(10):1675-82.
Huber O, Brunner A, Maier P, Kaufmann R, Couraud PO, Cremer C, Fricker G.Localization microscopy (SPDM) reveals clustered formations of P-glycoprotein in a human blood-brain barrier model. PLoS One. 2012;7(9):e44776.
Frank KJ, Rosenblatt KM, Westedt U, Hölig P, Rosenberg J, Mägerlein M, Fricker G, Brandl M.Amorphous solid dispersion enhances permeation of poorly soluble ABT-102: true supersaturation vs. apparent solubility enhancement. Int J Pharm. 2012 Nov 1;437(1-2):288-93.
Parmentier J, Thomas N, Müllertz A, Fricker G, Rades T.Exploring the fate of liposomes in the intestine by dynamic in vitro lipolysis. Int J Pharm. 2012 Nov 1;437(1-2):253-63
Anhalt K, Geissler S, Harms M, Weigandt M, Fricker G.Development of a new method to assess nanocrystal dissolution based on light scattering. Pharm Res. 2012 Oct;29(10):2887-901.
Frank KJ, Westedt U, Rosenblatt KM, Hölig P, Rosenberg J, Mägerlein M, Brandl M, Fricker G.Impact of FaSSIF on the solubility and dissolution-/permeation rate of a poorly water-soluble compound. Eur J Pharm Sci. 2012 Aug 30;47(1):16-20
Buckley ST, Fischer SM, Fricker G, Brandl M.In vitro models to evaluate the permeability of poorly soluble drug entities: challenges and perspectives. Eur J Pharm Sci. 2012 Feb 14;45(3):235-50.
Fischer SM, Buckley ST, Kirchmeyer W, Fricker G, Brandl M.Application of simulated intestinal fluid on the phospholipid vesicle-based drug permeation assay. Int J Pharm. 2012 Jan 17;422(1-2):52-8.
Mahringer A, Ott M, Reimold I, Reichel V, Fricker G.The ABC of the blood-brain barrier - regulation of drug efflux pumps. Curr Pharm Des. 2011;17(26):2762-70
Fischer SM, Flaten GE, Hagesæther E, Fricker G, Brandl M.In-vitro permeability of poorly water soluble drugs in the phospholipid vesicle-based permeation assay: the influence of nonionic surfactants. J Pharm Pharmacol. 2011 Aug;63(8):1022-30.
Parmentier J, Thewes B, Gropp F, Fricker G.Oral peptide delivery by tetraether lipid liposomes. Int J Pharm. 2011 Aug 30;415(1-2):150-7.
Fischer SM, Brandl M, Fricker G.Effect of the non-ionic surfactant Poloxamer 188 on passive permeability of poorly soluble drugs across Caco-2 cell monolayers. Eur J Pharm Biopharm. 2011 Oct;79(2):416-22.
Fischer SM, Brandl M, Fricker G. Effect of the non-ionic surfactant Poloxamer 188 on passive permeability of poorly soluble drugs across Caco-2 cell monolayers. Eur J Pharm Biopharm. 2011 Apr 28, epub ehead of print
Neuwelt EA, Bauer B, Fahlke C, Fricker G, Iadecola C, Janigro D, Leybaert L, Molnár Z, O'Donnell ME, Povlishock JT, Saunders NR, Sharp F, Stanimirovic D, Watts RJ, Drewes LR.
Engaging neuroscience to advance translational research in brain barrier biology. Nat Rev Neurosci. 12:169-82 (2011).
Parmentier J, Becker MM, Heintz U, Fricker G. Stability of liposomes containing bio-enhancers and tetraether lipids in simulated gastro-intestinal fluids. Int J Pharm. 405:210-7 (2011)
Berger FI, Feld J, Bertow D, Eisenbrand G, Fricker G, Gerhardt N, Merz KH, Richling E, Baum M. Biological effects of acrylamide after daily ingestion of various foods in comparison to water: a study in rats. Mol Nutr Food Res. 55:387-99 (2011).
MacLean C, Moenning U, Reichel A, Fricker G. Regional absorption of fexofenadine in rat intestine. Eur J Pharm Sci. 41:670-4 (2010).
Reichel V, Kläs J, Fricker G, Masereeuw R. Fluo-cAMP is transported by multidrug resistance-associated protein isoform 4 in rat choroid plexus. J Neurochem. 115(1):200-8 (2010).
Soomro S, Konkimalla VB, Langenberg T, Mahringer A, Horwedel C, Holenya P, Brand A, Catin C, Fricker G, Dewerchin M, Carmeliet P, Conway EM, Jansen H, Efferth T. Design of novel artemisinin-like derivatives with cytotoxic and anti-angiogenic properties. J Cell Mol Med. 2010 Jul 12. [Epub ahead of print]
Kanzer J, Hupfeld S, Vasskog T, Tho I, Hölig P, Mägerlein M, Fricker G, Brandl M. In situ formation of nanoparticles upon dispersion of melt extrudate formulations in aqueous medium assessed by asymmetrical flow field-flow fractionation. J Pharm Biomed Anal. 53:359-65 (2010).
Ofokansi K, Winter G, Fricker G, Coester C. Matrix-loaded biodegradable gelatin nanoparticles as new approach to improve drug loading and delivery. Eur J Pharm Biopharm. 76:1-9 (2010).
Fricker G, Kromp T, Wendel A, Blume A, Zirkel J, Rebmann H, Setzer C, Quinkert RO, Martin F, Müller-Goymann C. Phospholipids and lipid-based formulations in oral drug delivery. Pharm Res. 27:1469-86 (2010).
Tho I, Liepold B, Rosenberg J, Maegerlein M, Brandl M, Fricker G. Formation of nano/micro-dispersions with improved dissolution properties upon dispersion of ritonavir melt extrudate in aqueous media. Eur J Pharm Sci. 40:25-32 (2010).
Parmentier J, Hartmann FJ, Fricker G. In vitro evaluation of liposomes containing bio-enhancers for the oral delivery of macromolecules. Eur J Pharm Biopharm. 2010 Sep 16. Eur J Pharm Biopharm. 76:394-403 (2010)
Mahringer A, Fricker G. BCRP at the Blood-Brain Barrier: Genomic Regulation by 17β-Estradiol. Mol Pharm. 2010 Sep 9. [Epub ahead of print]
Kläs J, Wolburg H, Terasaki T, Fricker G, Reichel V. Characterization of immortalized choroid plexus epithelial cell lines for studies of transport processes across the blood-cerebrospinal fluid barrier. Cerebrospinal Fluid Res. 12;7:11 (2010)
Mahringer A, Karamustafa S, Klotz D, Kahl S, Konkimalla VB, Wang Y, Wang J, Liu HY, Boechzelt H, Hao X, Bauer R, Fricker G, Efferth T. Inhibition of P-glycoprotein at the blood-brain barrier by phytochemicals derived from traditional Chinese medicine. Cancer Genomics Proteomics. 7:191-205 (2010).
Reichel V, Kläs J, Fricker G, Masereeuw R. Fluo-cAMP is transported by multidrug resistance-associated protein isoform 4 in rat choroid plexus. J Neurochem. 115:200-8 (2010).
Kanzer J, Hupfeld S, Vasskog T, Tho I, Hölig P, Mägerlein M, Fricker G, Brandl M. In situ formation of nanoparticles upon dispersion of melt extrudate formulations in aqueous medium assessed by asymmetrical flow field-flow fractionation. J Pharm Biomed Anal. 53:359-65 (2010).
Ofokansi K, Winter G, Fricker G, Coester C. Matrix-loaded biodegradable gelatin nanoparticles as new approach to improve drug loading and delivery. Eur J Pharm Biopharm. 76:1-9 (2010).
Fricker G, Kromp T, Wendel A, Blume A, Zirkel J, Rebmann H, Setzer C, Quinkert RO, Martin F, Müller-Goymann C. Phospholipids and lipid-based formulations in oral drug delivery. Pharm Res. 27(8):1469-86 (2010).
Lechner C, Reichel V, Moenning U, Reichel A, Fricker G. Development of a fluorescence-based assay for drug interactions with human Multidrug Resistance Related Protein (MRP2; ABCC2) in MDCKII-MRP2 membrane vesicles. Eur J Pharm Biopharm. 75:284-90 (2010).
Sauer SW, Opp S, Mahringer A, Kamiński MM, Thiel C, Okun JG, Fricker G, Morath MA, Kölker S Glutaric aciduria type I and methylmalonic aciduria: simulation of cerebral import and export of accumulating neurotoxic dicarboxylic acids in in vitro models of the blood-brain barrier and the choroid plexus. Biochim Biophys Acta. 1802(6):552-60 (2010)..
Ott M, Huls M, Cornelius MG, Fricker G. St. John's Wort constituents modulate P-glycoprotein transport activity at the blood-brain barrier. Pharm Res. 27(5):811-22 (2010).
Tho I, Liepold B, Rosenberg J, Maegerlein M, Brandl M, Fricker G. Formation of nano/micro-dispersions with improved dissolution properties upon dispersion of ritonavir melt extrudate in aqueous media. Eur J Pharm Sci. 40(1):25-32 (2010).
Mahringer A, Delzer J, Fricker G. A fluorescence-based in vitro assay for drug interactions with breast cancer resistance protein (BCRP, ABCG2). Eur J Pharm Biopharm. 72(3):605-13 (2009).
Kühnle M, Egger M, Müller C, Mahringer A, Bernhardt G, Fricker G, König B, Buschauer A. Potent and selective inhibitors of breast cancer resistance protein (ABCG2) derived from the p-glycoprotein (ABCB1) modulator tariquidar. J Med Chem. 52(4):1190-7 (2009).
Mahringer A, Delzer J, Fricker G.A fluorescence-based in vitro assay for drug interactions with breast cancer resistance protein (BCRP, ABCG2). Eur J Pharm Biopharm. 72: 605-613 (2009).
Pinto A., Hoffmanns U., Fricker G., Metzler-Nolte N.: Modification with ferrocene carbox-ylic acid facilitates the membrane crossing of [Leu5]-Enkephaline derivatives in living systems. Chembiochem. 10:1852-1860 (2009).
Hülsermann U., Massing U., Hoffmann M., Fricker G. Uptake of Apolipoprotein E fragment coupled liposomes by cultured brain microvessel endothelial cells and intact brain capillaries. J. Drug Targeting 17: 610-618 (2009).
Ott, M., Fricker G., Bauer B.: PXR regulates P-glycoprotein at the Blood-Brain Barrier: Functional Similarities between Pig and Human PXR, J Pharmacol Exp Ther. 2009, 329: 141-149 (2009)
Krüger P., Kanzer J., Hummel J., Fricker G., Schubert-Zsilavecz M., Abdel-Tawab M.: Intestinal absorption Boswellia extract and interaction of its constituents KBA and AKBA with OATP 1B3 and MRP2. Eur. J. Pharm. Biopharm. 36:275-84 (2009)
Kühnle, M., Egger, M., Müller C., Mahringer, A., Bernhardt, G., Fricker, G., König, B.,Buschauer, A.: Potent and selective inhibitors of breast cancer resistance protein (ABCG2) derived from the p-glycoprotein (ABCB1) modulator tariquidar. J Med Chem. 26;52:1190-7 (2009).
Reimold I., Domke D., Bender J., Seyfried C. A., Radunz H.-E., Fricker G.: A nanoscaled approach to target the central nervous system. Eur. J. Pharm. Biopharm. 70, 627-632 (2008)
Reichel V., Miller D.S., Fricker G.: Transport of Texas Red in tubules of killifish and rat kidney. Am. J. Physiol. 295, R1311-1319 (2008)
MacLean C., Moenning U., Reichel A., Fricker G.: Closing the gaps - A full-scan of the intestinal expression of Pgp, Bcrp and Mrp2 in male and female rats. Drug Metabolism and Disposition, 36, 1249-1254(2008)
Mitschke D., Reichel A., Fricker G., Moenning U.: Characterization of Cytochrome P450 enzyme expression along the entire length of the intestine of male and female rats. Drug Metabolism and Disposition 36:1039-1045 (2008).
Förster F., Volz A., Fricker G.: Compound profiling for ABCC2 (MRP2) using a fluorescent microplate assay system. Eur J Pharm Biopharm. 69:396-403 (2008)
Adams M., Mahringer A., Kunerta O., Fricker G., Efferth T., Bauer R.: Cytotoxicity and P-Glycoprotein modulating effects of Quinolones and Indoloquinazolines from the Chinese herb Evodia rutaecarpa. Planta Medica, 73, 1554-1557 (2007)
Adams M., Mahringer A., Bauer R., Fricker G., Efferth T.: In vitro cytotoxicity and P-Glycoprotein modulating effects of geranylated Furocoumarins from Tetradium denielli. Planta Medica 73, 1475-1478 ( 2007)
Reichel V., BAehr C., Fricker G: From Blood to brain and vice versa: Transport processes in Choroid Plexus can be studied in vitro. ALTEX 24, Special issue, 53-55 (2007)
Reichel V, Masereeuw R, van den Heuvel JJ, Miller DS, Fricker G. Transport of a fluorescent cAMP analog in teleost proximal tubules. Am J Physiol Regul Integr Comp Physiol. 293:R2382-9 (2007)
Jarve A, Muller J, Kim IH, Rohr K, Maclean C, Fricker G, Massing U, Eberle F, Dalpke A, Fischer R, Trendelenburg MF, Helm M. Surveillance of siRNA integrity by FRET imaging. Nucleic Acids Res. 35(18):e124 (2007)
Bandara S., Diehl M., Fricker G.: A mathematical model for the transport of paclitaxel (Taxol) across the blood brain barrier. Chem. Engin. Res. Des. 85, 1-7, (2007)
Sauer SW, Okun JG, Fricker G, Mahringer A, Muller I, Crnic LR, Muhlhausen C, Hoffmann GF, Horster F, Goodman SI, Harding CO, Koeller DM, Kolker S. Intracerebral accumulation of glutaric and 3-hydroxyglutaric acids secondary to limited flux across the blood-brain barrier constitute a biochemical risk factor for neurodegeneration in glutaryl-CoA dehydrogenase deficiency. J Neurochem. 97:899-910 (2006)
Bubik M, Ott M, Mahringer A, Fricker G. Rapid assessment of p-glycoprotein-drug interactions at the blood-brain barrier. Anal Biochem. 358:51-58 (2006)
Baehr C, Reichel V, Fricker G. Choroid plexus epithelial monolayers - a cell culture model from porcine brain. Cerebrospinal Fluid Res. 21;3:13 (2006)
Baehr C, Fricker G, Miller DS. Fluorescein-Methotrexate Transport in Dogfish Shark (Squalus acanthias) Choroid Plexus. Am J Physiol Regul Integr Comp Physiol., 291:R464-72 (2006)
Ballatori N, Henson JH, Seward DJ, Cai SY, Runnegar M, Fricker G, Miller DS, Boyer JL Retention of structural and functional polarity in cultured skate hepatocytes undergoing in vitro morphogenesis Comp Biochem Physiol B Biochem Mol Biol. 44:167-179 (2006)
Flaig R., Rosenkranz V., Wink, M., Fricker G.: Ktenate Nanoparticels (Bdellosomes) : A novel strategy for targeting drugs to parasites, tumours or tissues. Drug Del. Sci Technol. 15, 59-63 (2005)
Rothkopf Ch., Fahr A., Fricker G., Scherphof G., Kamps J.A.A.M.: Liposomal liver perfusion and lipid/protein interactions. Biophys. Biochem. Acta, 1668, 10-16 (2005)
Hartz AM, Bauer B, Fricker G, Miller DS. Rapid modulation of P-glycoprotein-mediated transport at the blood-brain barrier by tumor necrosis factor-alpha and lipopolysaccharide. Mol Pharmacol. 69:462-70 (2005).
Weber CC, Kressmann S, Ott M, Fricker G, Muller WE Inhibition of P-glycoprotein function by several antidepressants may not contribute to clinical efficacy. Pharmacopsychiatry. 38,293-300 (2005).
Weber CC, Kressmann S, Fricker G., Muller WE: Modulation of p-glycoprotein function by St. John´s wort extract and its major constituents. Pharmacopsychiatry 37, 292-298 (2004)
Bauer B., Hartz A., Fricker G., Miller D.S.: Pregnane X receptor up-regulation of p-glycoprotein expression and transport function p-glycoprotein at the blood brain barrier. Molec. Pharmacol. 66, 413-419 (2004)
Hartz A., Bauer B., Fricker G, Miller DS: Rapid regulation of p-glycoprotein at the blood brain barrier by Endothelin-1. Molec. Pharmacol. 66, 387-394 (2004)
Breen C.M., Sykes D.B., Baehr C., Fricker G., Miller D.S.: Fluoresceinmethotrexate transport in intact rat choroid plexus. Am. J. Physiol., 287, F562-569 (2004)
Oude Elferink R., Ottenhoff R., Fricker G., Seward D.J., Ballatori N., Boyer J.L.: Lack of biliary lipid excretion in the little skate, Raja erinacea, indicates the absence of functional Mdr2, Abcg5, and Abcg8 transporters. Am. J. Physiol 286, G762-768 (2003)
Bauer B., Miller, D.S., Fricker G.: Compound profiling for p-glycoprotein at the blood-brain barrier using a microplate screening system. Pharm. Res. 20, 1170 – 1176 (2003)
Erdlenbruch B., Alipour M., Fricker G., Miller D.S., Kugler W., Eibl H., Lakomek M.: Opening of the blood-brain barrier to small and large fluorescence markers in normal and C6 glioma bearing rats and isolated rat brain capillaries using intracarotid short chain alkylglycerols, Brit. J. Pharmacol. 140, 1201-1210 (2003)
Török M., Huwyler J., Gutmann H., Fricker G., Drewe, J.: Modulation of transendothelial permeability and expression of ABC-transporters in cultured brain capillary endothelial cells by astrocytic factors and cell culture conditions. Exp. Brain Res. 221, 356-365 (2003)
Fellner S., Bauer B., Miller DS., Schaffrik M., Fankhänel M., Spruß T., Bernhardt G., Graeff C., Färber L., Gschaidhammer H., Buschauer A., Fricker G.: Transport of Paclitaxel (Taxol) across the blood brain barrier in vitro and in vivo. J. Clin. Invest., 110, 1309-1318 (2002)
Ritter M., Buechler C., Boettcher A., Barlage S., Schmitz-Madry A., Maa Bared S., Schmiedeknecht G., Baehr C., Fricker G., Schmitz G.: Cloning and characterization of a novel apolipoprotein A-I binding protein, AI-BP, secreted by cells of the kidney proximal tubules in response to HDL or ApoA-I. Genomics 79, 693-702 (2002)
Terlouw S. A., Graeff C., Fricker G., Masereeuw R., Russel F.G.M., Miller D.S.: Short- and long-term influences of heavy metals on anionic drug efflux from renal proximal tubule. J. Pharmacol. Exp. Ther. 301, 578-585 (2002)
Huwyler J., Cerletti A., Fricker G., Eberle A., Drewe J.: By-Passing of p-glycoprotein effect on digoxin uptake by immunoliposomes J. Drug Targeting 10, 73-79 (2002)
Breen C., Sykes D.B., Fricker G., Miller D.S.: Confocal imaging of organic anion transport in intact rat choroid plexus. Am. J. Physiol. 282, F877-F885 (2002)
Fricker G., Nobmann S., Miller DS.: Permeability of porcine blood brain barrier to somatostatin analogs. Brit. J. Pharmacol. 135, 1308-1314 (2002)
Miller D.S., Graeff C., Droulle L., Fricker S., Fricker G.: Xenobiotic efflux pumps in isolated fish brain capillaries. Am. J. Physiol. 282, R191-198 (2002)
Thöle M., Huwyler J., Fricker G.: Uptake of cationized albumin coupled liposomes by cultured brain microvessel endothelial cells and intact brain capillaries. J. Drug Targeting 10, 337-344 (2002)
Drewe J., Beglinger C., Fricker G.: Effect of ischemia on intestinal permeability of lipopoly-saccharides. Europ. J. Clin. Invest 31, 138-144 (2001)
Nobmann S., Bauer B., Fricker G.: Ivermectin excretion by isolated functionally intact brain endothelial capillaries. Brit. J. Pharmacol. 132, 722-728 (2001)
Miller D.S., Nobmann S., Gutmann H., Drewe J., Fricker G.: Xenobiotic transport in isolated brain microvessels studied by confocal microscopy. Molec. Pharmacol. 58, 1357 – 1367 (2000)
Cerletti A., Drewe J., Fricker G. , Eberle A., Huwyler J.: Endocytosis and transcytosis of an immunoliposome-based brain drug delivery system. J. Drug Targeting 8, 435-447 (2000)
Monella D., Sommer K., Fricker G., Völker U.: Comparative studies on particle size analysis. Chem. Ing. Tech. 72, 273-276 (2000)
Michael S., Thöle M., Dillmann R., Fahr A., Drewe J., Fricker G.: Improvement of intestinal peptide absorption by a synthetic bile acid derivative, cholylsarcosine. Europ. J. Pharm. Sci. 10, 133-140 (2000)
Gutmann H., Miller D.S., Droulle A., Drewe J., Fahr, A., Fricker G.: P-glyco-protein and mrp2 -mediated octreotide transport in renal proximal tubule. Brit. J. Pharmacol. 129, 251-256 (2000)
Fricker G., Gutmann H., Droulle A., Drewe J., Miller D.S.: Epithelial transport of anthelmintic ivermectin in a novel model of isolated proximal kidney tubules. Pharm. Res. 16, 1570-1575 (1999)
Gutmann H., Fricker G., Drewe J., Török M., Miller D.S.: Interactions of HIVprotease inhibitors with multiple ATP-dependent drug export proteins. Mol. Pharmacol. 56, 383-389 (1999)
Gutmann H., Török M., Fricker G., Huwyler J., Beglinger C., Drewe J.: Modulation of MRP expression in porcine brain capillary endothelial cells in vitro. Drug Metab. Disp. 27, 937-941 (1999)
Drewe J., Gutmann H., Fricker G., Török M., Beglinger C., Huwyler J.: HIV protease inhibitor ritonavir: A more potent inhibitor of p-glycopotein than the cyclo-sporine analogue SDZ PSC-833. Biochem. Pharmacol. 57: 1147-1152 (1999).
Török M., Gutmann H., Fricker G., Drewe J.: Sister of P-Glycoprotein Expression in Different Tissues. Biochem. Pharmacol. 57, 833-835 (1999)
Gutmann H., Drewe, J., Török M., Michael S., Beglinger C., Fricker G.: Evidence for different ABC-transporters in Caco-2 cells modulating drug uptake. Pharm. Res. 16, 402-407 (1999)
Török M., Huwyler J., Drewe J., Gutmann H., Fricker G.: Transport of the ß-lac-tam antibiotic benzylpenicillin and the dipeptide glycylsarcosine by brain capillary endothelial cells in vitro. Drug Metab. Disp. 26, 1144-1148 (1998)
Wolf A., Fahr, A., Schramm, U., Aicher J, Trommer, E, Cordier, A., Fricker, G.: Hepatocellular effects of cyclosporin A and its novel derivative SDZ IMM-125 in vitro. J. Pharmacol. Exp. Ther. 284, 817-825 (1998)
Fricker G., Miller, D., Drewe, J.: Role of p-Glycoprotein in the renal transport of rapamycin. Int. J. Clin. Pharmacol. Ther. 36, 12, 67-69 (1998)
Fricker G., Fahr A.: Mechanisms of hepatic transport of cylosporin A - an explanation of its cholestatic action? Yale Journal of Biology and Medicine 70, 379-390 (1997)
Fricker G., Woessner R., Drewe, J., Fricker, R., Boyer J.L.: Enterohepatic circulation of scymnol sulfate in an elasmobranch, the little skate (Raja erinacea). Am J Physiol. 273:G1023-30 (1997)
Miller D., Fricker G. Drewe J.: p-Glycoprotein mediated transport of a fluorescent rapamycin derivative in renal proximal tubule. J. Pharmacol. Exp. Therap. 282, 440-444, (1997)
Huwyler J., Fricker G., Török M., Schneider M., Drewe J.: Transport of clonidine across cultured brain microvessel endothelial cells. J. Pharmacol. Exp. Ther. 282, 81-85, (1997)
Fricker G., Küsters E.: Intestinal absorption of sugar-coupled somatostatin analogs. J. Pharm. Sci. 85: 1211-1214 (1996)
Urwyler S, Campbell E, Fricker G, Jenner P, Lemaire M, McAllister KH, Neijt HC, Park CK, Perkins M, Rudin M, Sauter A, Smith L, Wiederhold KH, Müller W. Biphenyl-derivatives of 2-amino-7-phosphono-heptanoic acid, a novel class of potent competitive N-methyl-D-aspartate receptor antagonists--II. Pharmacological characterization in vivo.Neuropharmacology. 35:655-69 (1996)
Oechslein C.R., Fricker G., Kissel T.: Nasal delivery of octreotide: Absorption enhancement by particulate carrier systems. Int. J. Pharmaceut. 139: 25-32 (1996)
Miller D., Fricker G., Schramm U., Henson J. H., Hager D. N., Nundy S., Ballatori N., Boyer J.L.: Active, microtubule-dependent secretion of a fluorescent bile salt derivative in skate hepatocyte clusters. Am. J. Physiol. 270: G887-G896 (1996)
Huwyler J., Drewe J., Kluseman C., Fricker G.: Evidence for P-glycoprotein-modulated penetration of morphine-6-glucuronide into brain capillary endothelium. Brit. J. Pharmacol. 118: 1879-1885 (1996)
Fricker G., Drewe J., Huwyler J., Gutmann H., Beglinger C.: Relevance of p-glycoprotein for the enteral absorption of cyclosporin A. In vitro - in vivo correlation. Brit. J. Pharmacol. 118: 1841-1847 (1996)
Haeberlin B., Gengenbacher T., Meinzer A., Fricker G.: Cyclodextrins – effective excipients for the oral administration of peptides? Int. J. Pharmaceut. 137: 103-110 (1996)
Fricker G., Drewe J., Fahr A., Kissel T., Beglinger C.: Permeation enhancement of octreotide by specific bile salts in rats and human subjects. In vitro - in vivo correlations. Brit. J. Pharmacol. 117: 217-223 (1996)
de Fraissinette A., Kolopp M., Schiller I., Fricker G., Gammert W., Pospischil A., Vonderscher J., Richter F.: In vitro tolerability of human nasal mucosa: Histopathological and scanning electron microscopic evaluation of nasal forms containing Sandostatin®. Cell Biol. and Toxicol. 11: 295-301 (1995)
Fahr A., Holz M., Fricker G.: Liposomal formulations of cyclosporin A: Influence of lipid type and dose on pharmacokinetics. Pharmaceut. Res. 12: 1189–1198 (1995)
Fricker G., Drewe J.: Enteral absorption of octreotide. Modulation of permeability by distinct carbohydrates. J. Pharmacol. Exp. Ther. 274: 826-832 (1995)
Billich A., Fricker G., Müller I., Donatsch P., Ettmayer P., Gstach H., Lehr P., Peichl P., Scholz D., Rosenwirth B.: SDZ PRI 053, an orally bioavailable human immunodefficiency virus type 1 proteinase inhibitor containing the 2-aminobenzyl-statine moiety. Antimicrobial Agents and Chemotherapy 39: 1406-1413 (1995)
Schramm U., Fricker G., Wenger R., Miller D.S.: p-Glycoprotein mediated transport of a fluorescent cyclosporin analogue in teleost proximal tubules. Am. J. Physiol. 268: F46-F52 (1995)
Billich A., Charpiot B., Fricker G., Gstach H., Lehr P., Peichl P., Scholz D., Rosenwirth B.: HIV proteinase inhibitors containing 2-aminobenzylstatine as a novel scissile bond replacement: Biochemical and pharmacological characterization. Antiviral Res. 25: 215-233 (1994)
Fricker G., Dubost V., Schwab D., Bruns C., Thiele C.: Heterogeneity in hepatic transport of somatostatin analogue octapeptides. HEPATOLOGY 20: 191-200 (1994)
Jaehde U., de Boer A.G., Masereeuw R., Fricker G., Nagelkerke J.F., Vonderscher J., Breimer D.D.: Quantification and visualization of the transport of octreotide, a somatostatin analogue, across monolayers of cerebrovascular endothelial cells. Pharmaceut. Res. 11: 442-448 (1994)
Fricker G., Dubost V., Finsterwald K., Boyer J. L.: Characteristics of bile salt uptake into skate hepatocytes. Biochem. J. 299: 665-670 (1994)
Albert R., Marbach P., Bauer W., Briner U., Fricker G., Bruns C., Pless J.: SDZ CO 611: A highly potent glycated analogue of somatostatin with improved oral activity. Life Sci. 53: 517 - 525 (1993)
Bossard R., Stieger B., O'Neill B., Fricker G., Meier P.: Ethinylestradiol (EE) treatment induces multiple canalicular membrane transport alterations in rat liver. J. Clin. Invest. 91: 2714 - 2720 (1993)
Schramm U., Fricker G., Buscher H.-P., Gerok W., Kurz G.: Fluorescent derivatives of bile salts. III. Uptake of 7b-NBD-NCT into isolated hepatocytes by the transport systems for cholyltaurine. J. Lipid Res. 34: 741 - 757 (1993)
Drewe J., Fricker G., Vonderscher J., Beglinger C.: Enteral absorption of octreotide. Absorption enhancement by polyoxyethylene-24-cholesterol ether. Brit. J. Pharmacol. 108: 298 - 303 (1993)
Fricker G., Drewe J., Vonderscher J., Kissel T., Beglinger C.: Enteral absorption of octreotide. Brit. J. Pharmacol. 105: 783-786 (1992)
Fricker G., Bruns C., Munzer J., Briner U., Albert R., Kissel T., Vonderscher J.: Intestinal absorption of the octapeptide SMS 201-995 visualized by fluorescence derivatization. Gastroenterology 100: 1544-1552 (1991)
Fricker G., Landmann L., Meier P.J.: Extrahepatic obstructive cholestasis reverses the bile salt secretory polarity of rat hepatocytes. J. Clin. Invest. 84: 876-885 (1989)
Fricker G., Hugentobler G., Meier P.J., Kurz G., Boyer J.L.: Identification of a single sinusoidal bile salt uptake system in skate liver. Am. J. Physiol. 253: G816-G822 (1987)
Hugentobler G., Fricker G., Boyer J.L., Meier P.J.: Anion transport in basolateral (sinusoidal) liver plasma membrane vesicles of the little skate (Raja erinacea). Biochem. J. 247: 589-595 (1987)
Fricker G., Schneider S., Gerok W., Kurz G.: Identification of different transport systems for bile salts in sinusoidal and canalicular membranes of hepatocytes. Biol Chem Hoppe Seyler. 368:1143-50 (1987).
Ruetz S., Fricker G., Hugentobler G., Winterhalter K., Kurz G., Meier P.J.: Identification and characterization of the putative canalicular bile salt transport system of rat liver. J. Biol. Chem. 262: 11324-11330 (1987)
Kröncke K.D., Fricker G., Meier P.J. Gerok W., Wieland T., Kurz G.: a-Amanitin uptake into hepatocytes; identification of hepatic membrane transport systems used by amatoxins. J. Biol. Chem. 261: 12562-12567 (1986)
Wieland T., Nassal M., Kramer W., Fricker G., Bickel U., Kurz G.: Identity of hepatic membrane transport systems for bile salts, phalloidin, and antamanide by photoaffinity labeling. Proc. Natl. Acad. Sci. USA 81: 5232-5236 (1985)
