DE Research aerea
Prof. Dr. Gert Fricker
Prof. Dr. Gert Fricker
Director
Dept. Pharmaceutical Technology and Biopharmacy
Institute of Pharmacy and Molecular Biotechnology
- +49 6221 54 8330
- +49 6221 54 5971
- gert.fricker@uni-hd.de
Dr. Gert Fricker is Director of the Institute of Pharmacy and Molecular Biotechnology at the Faculty of Biosciences of the University of Heidelberg, Germany.
After studying chemistry and medicine at the University of Freiburg, Germany, and completing his doctorate in 1986, he worked as a post-doctoral fellow in the Department of Clinical Pharmacology at the University Hospital Zurich, Switzerland.
In 1988 he became a research associate at Sandoz Pharma AG, Basel, Switzerland. As a member of the Drug Delivery Systems department, he investigated the mechanisms of drug permeation through barrier tissue.
In 1995, G. Fricker was appointed professor at the University of Heidelberg, and in 2002 he took over the chair of pharmaceutical technology and became director of the Institute of Pharmacy and Monekluare biotechnology. In addition to his university work, G. Fricker is head of the Steinbeis Technology Transfer Center for Biopharmacy & Analytics in Heidelberg, a service center for the pharmaceutical industry, and co-founder of Heidelberg Delivery Technologies GmbH, HeiDelTec, a start-up company that deals with oral peptide administration. His research focuses on the permeation of drugs through barrier tissue with a particular focus on the intestine and blood-brain barrier as well as the development of drug targeting systems using colloidal drug carriers.
| Career | since 2017 Co-founder of the Heidelberg Delivery Technologies GmbH, HEIDELTEC, a company for oral peptide and protein delivery since 2002 Director of the Institute of Pharmacy and Molecular Biotechnology of the Faculty for Bio-Sciences at the University of Heidelberg since 1988 CEO of the Steinbeis-Technology Transfer Center Biopharmacy and Analytics in Heidelberg (industrial contract work) 1997- 2002 Director of the „Institut für Pharmazeutische Technologie und Biopharmazie“, Faculty of Pharmacy, University of Heidelberg 1995 – 2002 Professor at the „Institut für Pharmazeutische Technologie und Biopharmazie“ Faculty of Pharmacy, University of Heidelberg 1988 – 1995 Research Scientist, Dept. Drug Delivery Systems, Sandoz Pharma AG, Basel, CH 1986 – 1988 Post-Doc at the University Hospital Zürich, Switzerland; Clin. Pharmacology, |
| Academic Education | 1975 – 1986
PhD ; Thesis: Transcellular Transport of Bile Acids in the Liver 1993 Habilitation and venia legendi for ‚Experimental Medicine‘, University of Freiburg; Thesis: Pathomechanisms of obstructive Cholestasis and Estradiol induced intrahepatic Cholestasisseit |
| Focus of research | Drug transport across Blood Brain Barrier Hepatic transport mechanisms Membrane transport mechanisms ABC-Transporter – Verbesserung der Arzneimittelabsorption und gezielter Einsatz von Arzneimitteln Drug formulation |
| Auszeichnungen / Preise | Phoenix Pharmacy Science Awards for outstanding scientific contributions in Pharmaceutical Technology/Pharmacology (2003,2008) Dietrich-Schmähl Award of the Central European Society for Anticancer Drug Research (2003) Research Award of the Association of Pharmaceutical Technology (APV) for outstanding scientific achievements in Pharmacy (1998) |
| publications | more than 220 publications in peer reviewed journals more than 60 contributions for books and other publications |
Career
since 2017
Mitbegründer der Heidelberg Delivery Technologies GmbH, HEIDELTEC, einem Unternehmen für orale Peptid- und Proteinverabreichung
since 2002
Director of the Institute of Pharmacy and Molecular Biotechnology of the Faculty for Bio-Sciences at the University of Heidelberg
since 1988
CEO of the Steinbeis-Technology Transfer Center Biopharmacy and Analytics in Heidelberg (industrial contract work)
1997- 2002
Director of the „Institut für Pharmazeutische Technologie und Biopharmazie“, Faculty of Pharmacy, University of Heidelberg
1995 – 2002
Professor am „Institut für Pharmazeutische Technologie und Biopharmazie“, Fakultät für Pharmazie, Universität Heidelberg
1988 – 1995
Research Scientist, Dept. Drug Delivery Systems, Sandoz Pharma AG, Basel, CH
1986 – 1988
Post-Doc at the University Hospital Zürich, Switzerland; Clin. Pharmacology,
Academic Education
1975 – 1986
University of Freiburg im Breisgau, Germany – Chemistry, Medicine
1986
PhD ; Thesis: Transcellular Transport of Bile Acids in the Liver
1993
Habilitation and venia legendi for ‚Experimental Medicine‘, University of Freiburg; Thesis: Pathomechanisms of obstructive Cholestasis and Estradiol induced intrahepatic Cholestasisseit
Focus of research
Drug transport across Blood Brain Barrier
Hepatic transport mechanisms
Membrane transport mechanisms
ABC transporter drug absorption enhancement and drug targeting
Drug formulation
publications
more than 220 publications in peer reviewed journals
more than 60 contributions for books and other publications
12 patent applications
2023
Titel: EURAS: European network for neurodevelopmental Rasopathies
Funding amount: 8.500.000 €
Sponsor: European Union
2022
Titel: Stabilization of Lyso-Phosphatidylcholine-levels in patients with cancer
Funding amount: 135.600 €
Sponsor: Phospholipid Research Center Heidelberg
2021
Titel: Delivery of Biologicals across the Blood-Brain Barrier
Funding amount: 498.060 €
Sponsor: Baden-Württemberg Foundation, Programm „Internationale Spitzenforschung“
2021
Titel: BrainAim – Delivery of bifunctional antibodies across the blood brain barrier
Funding amount: 1.726.236 € (4 Research Groups)
Sponsor: Federal Ministry of Education and Research, Germany
2021
Titel: MunaVac – Development of a novel delivery system for mucosal HPV-vaccination
Funding amount: 991.632 € (3 Research Groups)
Sponsor: Federal Ministry of Education and Research, Germany
2019
Titel: IM2PACT – Investigating Mechanisms and Models Predictive of Accessibility of Therapeutics into The Brain
Funding amount: 18.000.000 € (25 Research Groups)
Sponsor: European Union: Program “Innovative Medicines Initiative 2 Joint”
Drug transport through the blood-brain barrier
Many potentially highly potent CNS-active drugs are unable to cross the blood-brain barrier because their polarity prevents them from penetrating the lipid barrier of brain capillary endothelial cells and/or because they are recognized by active transport systems in the endothelial cells and transported back into the bloodstream.
These transport systems will be identified at the molecular level and their function and expression as well as their role in drug transport will be investigated.
Particular attention is paid to the ABC (ATP binding cassette) export proteins.
The transport proteins are investigated in primary cell cultures from brain capillary endothelial cells, immortalized cell lines, isolated and functionally intact brain capillaries and in vivo in rats.
Drug Targeting
Development of colloidal carrier systems (nanoparticles, liposomes) with which non-permeable active ingredients can be introduced into the brain through capillary endothelial cells. These carrier systems are coupled to target-seeking vectors (e.g. antibodies) that recognize certain receptors on the blood-brain barrier and are introduced into the brain via these receptors through the capillary endothelium through transcytosis.
The project is carried out in collaboration with the University of Basel (Switzerland), the University of Frankfurt and partners from industry.
Development of predictive in vitro models for the investigation of transport mechanisms
Molecular mechanisms of cellular transport can hardly be investigated in vivo. The aim of the project is therefore to improve existing in vitro models with regard to their predictive character and to establish new models. The investigations focus on models for testing intestinal resorption processes and models of capillary endothelial cells for simulating the blood-brain barrier.
Improving drug absorption from the gastrointestinal tract
Poorly soluble active ingredients and peptide drugs can hardly be administered orally, as they are rapidly broken down in the gastrointestinal tract or only absorbed in very small quantities. Ways are being sought to improve their solubility and absorption through the intestinal wall without damaging the intestinal mucosa.
The dosage forms investigated are microemulsion systems, lipid nanoparticle systems and liposomal systems.
Cellular transport systems
In this project, membrane transport systems for organic anions and cations in the blood-brain barrier and in the choroid plexus and in the kidney are investigated functionally and at the molecular level. Isolated membrane fractions, isolated cells and whole, functionally intact pieces of tissue are used to test whether membrane transporters that transport physiologically present organic anions or cations also have an affinity for certain pharmaceuticals.
The results obtained in the in vitro models are correlated with pharmacokinetic in vivo findings.
Parts of these studies were conducted during annual research stays of several months at the Mount Desert Island Biological Labroratory (mdibl.org), Salsbury Cove, Maine, USA.
Collaborations
-
T. Terasaki | Japan
Tohoku University, Sendai -
M. Udenäs - Hammarlund | Schweden
Universität Uppsala -
M. Brandl | Dänemark
Universität Odense -
J. Huwyler | Schweiz
Universität Basel -
H. Kidron | Finnland
Universität Helsinki -
H. Haller | USA
MDI Biological Laboratory
Selected publications
Textbook
Biopharmazie
P. Langguth, G. Fricker, H. Wunderli-Allenspach
VCH-Wiley, 2004
- Puris E, Petralla S, Auriola S, Kidron H, Fricker G, Gynther M. Monoacylglycerol Lipase Inhibitor JJKK048 Ameliorates ABCG2 Transporter-Mediated Regorafenib Resistance Induced by Hypoxia in Triple Negative Breast Cancer Cells. J Pharm Sci. 2023:S0022-3549(23)00198-3. doi: 10.1016/j.xphs.2023.05.012.
- Eteläinen TS, Silva MC, Uhari-Väänänen JK, De Lorenzo F, Jäntti MH, Cui H, Chavero-Pieres M, Kilpeläinen T, Mechtler C, Svarcbahs R, Seppälä E, Savinainen JR, Puris E, Fricker G, Gynther M, Julku UH, Huttunen HJ, Haggarty SJ, Myöhänen TT. A prolyl oligopeptidase inhibitor reduces tau pathology in cellular models and in mice with tauopathy. Sci Transl Med. 2023;15(691):eabq2915. doi: 10.1126/scitranslmed.abq2915.
- Puris E, Fricker G, Gynther M.The Role of Solute Carrier Transporters in Efficient Anticancer Drug Delivery and Therapy. Pharmaceutics. 2023 Jan 21;15(2):364. doi: 10.3390/pharmaceutics15020364.
- Puris E, Saveleva L, de Sousa Maciel I, Kanninen KM, Auriola S, Fricker G. Protein Expression of Amino Acid Transporters Is Altered in Isolated Cerebral Microvessels of 5xFAD Mouse Model of Alzheimer’s Disease. Mol Neurobiol. 2023;60(2):732-748. doi: 10.1007/s12035-022-03111-y.
- Gynther M, Estrada ML, Loppi S, Korhonen P, Kanninen KM, Malm T, Koistinaho J, Auriola S, Fricker G, Puris E. Increased Expression and Activity of Brain Cortical cPLA2 Due to Chronic Lipopolysaccharide Administration in Mouse Model of Familial Alzheimer’s Disease. Pharmaceutics. 2022;14(11):2438. doi: 10.3390/pharmaceutics14112438.
- Oezen G, Schentarra EM, Bolten JS, Huwyler J, Fricker G. Sodium arsenite but not aluminum chloride stimulates ABC transporter activity in renal proximal tubules of killifish (Fundulus heteroclitus). Aquat Toxicol. 2022;252:106314.
doi: 10.1016/j.aquatox.2022.106314. - Wupperfeld D, Fricker G, Bois De Fer B, Frank L, Wehrle A, Popovic B. Essential phospholipids decrease apoptosis and increase membrane transport in human hepatocyte cell lines. Lipids Health Dis. 2022 Sep 24;21(1):91. doi: 10.1186/s12944-022-01698-8.
- Zoeller MP, Hafiz S, Marx A, Erwin N, Fricker G, Carpenter JF Exploring the Protein Stabilizing Capability of Surfactants Against Agitation Stress and the Underlying Mechanisms. J Pharm Sci. 2022;111(12):3261-3274. doi: 10.1016/j.xphs.2022.09.004.
- Puris E, Auriola S, Petralla S, Hartman R, Gynther M, de Lange ECM, Fricker G. Altered protein expression of membrane transporters in isolated cerebral microvessels and brain cortex of a rat Alzheimer’s disease model.Neurobiol Dis. 2022;169:105741. doi: 10.1016/j.nbd.2022.105741.
- Keller BL, Lohmann CA, Kyeremateng SO, Fricker G. Synthesis and Characterization of Biodegradable Poly(butyl cyanoacrylate) for Drug Delivery Applications. Polymers (Basel). 2022;14(5):998. doi: 10.3390/polym14050998.
- Balzer V, Poc P, Puris E, Martin S, Aliasgari M, Auriola S, Fricker G. Re-evaluation of the hCMEC/D3 based in vitro BBB model for ABC transporter studies. Eur J Pharm Biopharm. 2022;173:12-21. doi: 10.1016/j.ejpb.2022.02.017.
- Bolten JS, Pratsinis A, Alter CL, Fricker G, Huwyler J.Zebrafish (Danio rerio) larva as an in vivo vertebrate model to study renal function. Am J Physiol Renal Physiol. 2022;322(3):F280-F294. doi: 10.1152/ajprenal.00375.2021.
- Lechner C, Mönning U, Reichel A, Fricker G. Potential and Limits of Kidney Cells for Evaluation of Renal Excretion. Pharmaceuticals (Basel). 2021;14(9):908. doi: 10.3390/ph14090908.
- Sironi D, Bauer-Brandl A, Brandl M, Rosenberg J, Fricker G. The influence of liquid intake on the performance of an amorphous solid dispersion in rats. Eur J Pharm Biopharm. 2020;152:296-298. doi: 10.1016/j.ejpb.2020.05.021.
- Lüchtenborg C, Niederhaus B, Brügger B, Popovic B, Fricker G. Lipid Profiles of Five Essential Phospholipid Preparations for the Treatment of Nonalcoholic Fatty Liver Disease: A Comparative Study.Lipids. 2020;55(3):271-278. doi: 10.1002/lipd.12236.
- Köthe T, Martin S, Reich G, Fricker G. Dual asymmetric centrifugation as a novel method to prepare highly concentrated dispersions of PEG-b-PCL polymersomes as drug carriers. Int J Pharm. 2020; 579:119087. doi: 10.1016/j.ijpharm.2020.119087.
- Mahringer A, Bernd A, Miller DS, Fricker G. Aryl hydrocarbon receptor ligands increase ABC transporter activity and protein expression in killifish (Fundulus heteroclitus) renal proximal tubules. Biol Chem. 2019;400(10):1335-1345. doi: 10.1515/hsz-2018-0425.
- Zaremba A, Helm F, Fricker G. Impact of Zn2+ on ABC Transporter Function in Intact Isolated Rat Brain Microvessels, Human Brain Capillary Endothelial Cells, and in Rat in Vivo.
- Mol Pharm. 2019;16(1):305-317. doi: 10.1021/acs.molpharmaceut.8b00987.
- Schmitt MV, Lienau P, Fricker G, Reichel. Quantitation of Lysosomal Trapping of Basic Lipophilic Compounds Using In Vitro Assays and In Silico Predictions Based on the Determination of the Full pH Profile of the Endo-/Lysosomal System in Rat Hepatocytes. Drug Metab Dispos. 2019;47(1):49-57. doi: 10.1124/dmd.118.084541.
