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I. Head of Research Group:
II. Senior Scientist:
III. Group Members: Graduate Students:
in collaboration with
IV. Group Members: Diploma Students:
in collaboration with  
V. Group Members: Technical Staff:
Overview - Research Activities:
The research focus of the institute is based on: Cellular Stress and Tissue Dysfunction which in detail involves:
- Cardiovascular Stress and Cytoprotective Drugs
- Anti-Infective and Anti-Inflammatory Drugs
- Anti-Cancer Drugs
- Pharmaceutical Micro- and Nano-Technology
Focus:
The main research interest of our group is focused on the development of pharmaceutical
preparations for nucleic acids and peptide drugs based on new approaches of pharmaceutical nanotechnology.
Nucleic acid drugs such as oligonucleotides, siRNA, are representing a new class of
substances used for several therapeutic targets including viral infections and cancer. In
contrast to the approach of gene therapy which involves the replacement and substitution of
genetic material, antisense drugs or siRNA do not alter or substitute the endogenous genetic material
during the antisense therapy. These oligonucleotides are effective blocking agents of the
protein expression with a high sequence specificity. Single stranded modified DNA oligonucleotides are often used in
typical antisense trials whereas siRNA is used more fequently in latest research projects.
Unfortunately, all oligonucleotide drugs - DNA or RNA -
are considered to be degraded by nucleases and they exhibit only a weak permeation through
biological cell membranes resulting a poor bioavailability. Therefore, a strong need exists for
delivery systems which protect the antisense drugs from enzymatic digestion and provide an
enhanced transfection to the cytoplasm of the target cells. Additionally, these carrier could be
active targeting instruments transporting the antisense drugs only to specific cell types of the
organism.
Until now, colloidal drug delivery systems based on liposomes and nanoparticles are under
evaluation. Cationically charged vesicles were found to be potent tools to create complex
structures between DNA and the lipid phase. Equivalent results were obtained for particles
based on acrylates and/or dextrans. Additionally, artificial viral capsid structures are an
innovative concept for antisense drug application and they appear to be an interesting new
drug delivery system.
The latest improvements in drug delivery are Protamine-Oligonucleotide-Particles - so called Proticles.
These colloids are potent transport vehicles for oligonucleotides as well as for peptides and proteins.
Several co-operations are initiated with other research groups located in Graz to investigate the purpose of
these promissing nanoparticles.
Research projects
- Pharmaceutical Nanotechnology: The projects are sponsored by the Austrian Nano Initiative,
the FWF and FFG. The projects are organized by
www.bionanonet.at . New peptide based delivery systems are under investigation as drug delivery systems and diagnostics.
These nanoparticles are called Proticles (Protamine-Oligonucleotide-Particles) and are an interesting new delivery approach for
antisense compounds, siRNA as well as for peptides and proteins. Current projects include stem cell tracking, VIP Depot formulations for pulmonary delivery, and are part of nanoHealth.
- Cellular test-systems are developed especially for siRNA constructs linked to proteins as carriers. Down-regulation of protein levels
are studied on a brain tumor model. Co-workers in this field are Wolfgang Sattler and Eva Bernhart, Medical University Graz. Funding is provided by the FFG Bridge Program.
- Pharmaceutical Engineering is the topic of the recently founded Competence Center RCPE. Project are focussed on upscaling of
nanoparticle production, protein formulations and new Drug Delivery Systems based on cellulose.
- EuroNanoTox is a project coordinated by the BionanoNet. Our contribution is based on literature databases available by nanoTRUST and in vitro toxicity tests for drug formulations.
- Depot-Formulations for colloidal drugs and special micropellets are a new research area founded in Graz. Currently drug
formulations based on lipophilic matrices dispersed in thixotropic liquids are under investigation.
- Antisense Therapy with Drug Delivery Vehicles of our group is combined with new strategies in Photodynamic Therapy against tumors.
This project was part of the Pharmacy DFG-Graduiertenkolleg at the Biocenter Frankfurt together with Manfred Schubert-Zsilavecz and the ILM, Ulm.
sponsored by:
Publications (2007 - 2012):
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Burian B., Ortner A., Prassl R., Zimmer A., Mosgoeller W.
Clinical potential of VIP by modified pharmako-kinetics and delivery mechanisms
Endocrine, Metabolic & Immune Disorders - Drug Targets (2012) in press |
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Roblegg E, Fröhlich E, Meindl C, Teubl B, Zaversky M, Zimmer A.
Evaluation of a physiological in-vitro system to study the transport of nanomaterials through the buccal mucosa
Nanotoxicology 6 (2012) 399-413 |
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Ablinger E., Wegscheider S., Keller W., Prassl R., Zimmer A.
Effect of protamine on the solubility and deamidation of human growth hormone
International Journal of Pharmaceutics 427 (2012) 209– 216. |
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Mosgoeller W., Prassl R., Zimmer A.
Nanoparticle-mediated treatment of pulmonary arterial hypertension
Methods in Enzymology 508 (2012) 325-354. |
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Roblegg, E., Falk, A., Fröhlich, E., Zimmer A., and Sinner, F.
European Centre for Nanotoxicology: A Proactive Risk-assessment Nanotechnology lnitiative
Academy of Science Malaysia Journal, 5 (1) (2011) 43-52. |
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T. Paukert, R. Sailer, W. S. L. Strauss, M. Schubert-Zsilavecz, Zimmer A.
Glutathione peroxidase isoenzymes in human tumor cell lines
Die Pharmazie 66 (2011) 894-898. |
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Pardeike J., Strohmeier D.M., Schrödl N., Vourab Ch., Gruber M., Khinast J., Zimmer A.
Nanosuspensions as advanced printing ink for accurate dosing of poorly soluble drugs in personalized medicines
International Journal of Pharmaceutics 420 (2011) 93-100. |
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Roblegg E., Jäger E., Hodzic A., Koscher G., Mohr S.,Zimmer A., Khinast J.
Development of sustained-release lipophilic calcium stearate pellets via hot
melt extrusion
European Journal of Pharmaceutics and Biopharmaceutics 79 (2011) 635–645. |
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Eitzlmayr A., Petschacher Ch., Radl S., Suzzi D., Zimmer A., Khinast J.G.
Modeling and Simulation of Polyacrylic acid/Protamine Nanoparticle Precipitation
Soft Matter 7 (2011) 9484-9497. |
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Roblegg, E., Schrank S., Griesbacher M., Radl S., Zimmer A., and Khinast J.
Use of the Direct Compression Aid Ludiflash® for the Preparation of Pellets via Wet Extrusion/Spheronization
Drug Development and Industrial Pharmacy 37 (2011) 1231-1243. |
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Pardeike, J., Weber, S., Haber, T., Wagner, J., Zarfl, H.P., Plank, H., Zimmer A.
Development of an Itraconazole-loaded Nanostructured Lipid Carrier (NLC) formulation for pulmonary application
International Journal of Pharmaceutics 419 (2011) 329– 338. |
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Stegemann S., Rasenack H., Ecker F., Zimmer A.
Geriatrische Arzneimitteltherapie: Gesellschaftliche Herausforderung und pharmazeutische Lösungsansätze
Deutsche Apotheker Zeitung 31 (2011) 44-58. |
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Almer G., Wernig K., Saba-Lepek M., Haj-Yahya S., Rattenberger J., Wagner J., Gradauer K., Frascione D., Pabst G., Leitinger G., Mangge H., Zimmer A., Prassl R.
Adiponectin-coated nanoparticles for enhanced imaging of atherosclerotic plaques
International Journal of Nanomedicine 6 (2011) 1279-1290. |
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Dittrich, P., Beubler, E., Haltmeyer, K., and Zimmer A., Roblegg E.
Pharmacokinetics of a Novel Liquid Controlled Release Codeine Formulation
Drug Development and Industrial Pharmacy (2011) |
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Voura, C., Gruber, M.M., Schroedl, N., Eitzinger, B., Bauer, W., Brenn, G., Khinast, J.G., Zimmer A.
Printable Medicines - A Microdosing Device for the Production of Personalized Oral Dosage Forms
Pharmaceutical Technology Europe 23 (1) (2011) 32-36. |
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Stegemann S., Ecker F., Maio M., Kraahs P., Wohlfart R., Breitkreuz J., Zimmer A., Bar-Shalom D.,
Hettrich P., and Broegmann B.
Geriatric drug therapy: neglecting the inevitable majority
Ageing Res Reviews 9 (4) (2010) 384-398. |
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Roblegg E., Dittrich P., Haltmeyer K., and Zimmer A.
Reformulation of a codeine phosphate liquid controlled release product
DDIP 36 (12) (2010) 1454-1462. |
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Ortner A., Wernig K., Kaisler R., Edetsberger M., Hajos F., Köhler G., Mosgoeller W. and Zimmer A.
VPAC receptor mediated tumour cell targeting by protamine based nanoparticles
J Drug Target 18 (6) (2010) 457-467. |
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Roblegg E., Ulbing S., Zeissmann S., and Zimmer A.
Development of lipophilic calcium stearate pellets using ibuprofen as model drug
EJPB 75 (1) (2010) 56-62. |
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Roblegg E., Sinner F. and Zimmer A.
Health Risks of Nanotechnology
Euro Nano Tox Letters (2009) 1-18. |
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Fröhlich E., Samberger C., Kueznik T., Absenger M., Roblegg E., Zimmer A. and Pieber Th. R.
Cytotoxicity of nanoparticles independent from oxidative stress
J Toxicol Sci 34 (2009) 363-375. |
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Budai M., Chapela P., Budai L., Wales M., Petrikovics I., Zimmer A., Grof P., Klebovich I. and Szilasi M.
Liposomal oxytetracycline and doxycycline: studies on enhancement of encapsulation efficiency.
Drug Discov Ther (2009) 13-17. |
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Budai M., Chapela P., Grof P., Zimmer A., Wales M., Wild JR., Klebovich I., Petrikovics I. and Szilasi M.
Physicochemical characterization of stealth liposomes encapsulating an organophosphate hydrolyzing enzyme.
J Liposome Res. 23 (2009) 1-6. |
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Reischl D. and Zimmer A.
Drug delivery of siRNA therapeutics: Potentials and limits of nanosystems
J Nanomed 5 (2009) 8-20. |
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Schicher M., Polsinger M., Hermetter A., Prassl R. and Zimmer A.
In vitro release of Propofol and binding capacity with regard to plasma constitutents
Eur J Pharm Biopharm 70 (2008) 882-888. |
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Kaszás N., Budai M., Budai L, Gróf P., Zimmer A., Klebovich I.
Methods to increase the encapsulation efficiency for liposomal drugs
Acta Pharm Hungarica 78 (2008) 69-74. |
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Wernig K., Griesbacher M., Andreae F., Hajos F., Wagner J., Mosgoeller W. and Zimmer A.
Depot formulation of Vasoactive Intestinal Peptide by protamine-based biodegradable nanoparticles
J Control Rel 130 (2008) 192-198. |
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Budai M., Gróf P., Zimmer A., Pápai K., Klebovich I. and Ludányi K
UV light induced photodegradation of liposome encapsulated fluoroquinolones: an MS study
J Photochem 198 (2008) 268-273. |
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Graf A., Ablinger E.; Peters S., Zimmer A., Hook S. and Rades Th.
Microemulsions containing lecithin and sugar-based surfactants: Nanoparticle templates for delivery of proteins and peptides
Int. J. Pharm. 350 (2008) 351-360. |
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Kratzer I., Wernig K., Panzenboeck U., Bernhart E., Reicher H., Wronski R., Windisch M., Hammer A., Malle E., Zimmer A., Sattler W.
Apolipoprotein A-I coating of protamine-oligonucleotide nanoparticles increases particle uptake and transcytosis in an in vitro model of the blood-brain barrier
J Control Release 117 (2007) 301-311. |
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List of all publications since 1987 ...
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Poster Presentation
Books and Electronic Publications
- Zimmer A.; Pharmacokinetics and Pharmacodynamics of pilocarpine loaded PBCA-
nanoparticles in the glaucomatous rabbit eye, Verlag Shaker, Aachen, ISBN 3-86111-
577-8 (1993)
- Zimmer A. und Herzfeldt C.-D.; CompaSys Dermatika, Govi-Verlag GmbH,
Pharmazeutischer Verlag, Eschborn, ISBN: 3-7741-0222-8, (1990), 2nd. Ed. (1994),
On-Disk-Database Version 3.5 (1996)
- Zimmer A. und Herzfeldt C.-D.; InfoSys Sonnenschutz, Govi-Verlag GmbH,
Pharmazeutischer Verlag, Eschborn, ISBN: 3-7741-0226-X, (1991), On-Disk-Database
Version 2.9 (1999).
- Zimmer A. und Herzfeldt C.-D.; InfoSys Handverkauf, Govi-Verlag GmbH,
Pharmazeutischer Verlag, Eschborn, ISBN: 3-7741-0267-8, (1992), On-Disk-Database
Version 2.2 (1996).
Book Chapters
Literature from recent diploma and undergraduate work:
- Zobel H.-P., Brinkmann I., Förstel B., Heim S., Müller Ch., Nguyen Th.H.V., Prescher K.
and Zimmer A. Das Unguator-Rührsystem (URSY) als Alternativverfahren zur Salbenherstellung,
Der Deutsche Dermatologe, 6 (1998) 545-549.
- Zimmer A., Kreuter J., Graeser U., and Wakolbinger A. Altarzneimittelstudie,
Pharm. Ztg., 3 (1999) 23-29.
- Deml A., Jennes I., Küster C., Preißmann M., Wingerter O., and Zimmer A., Insulinpumpen -
Technische und Pharmazeutische Anforderungen,
Deutsche Apoth. Ztg.140 (2000) 56-62.
- Lochmann, D., Stadlhofer, S., Weyermann, J., and Zimmer, A.,
New protamine quantification method in microtiter plates using o-phthaldialdehyde/N-acetyl-L-cysteine reagent,
International Journal of Pharmaceutics 283 (2004) 11-17.
Doctoral Dissertation Titles:
(in collaboration with Priv.-Doz. Dr. Bertling, Prof. Dr. Dingermann, Prof. Dr. Dr. Fasold, Prof. Dr. Haslinger, Prof. Dr. Kreuter, Prof. Dr. Noe, Prof. Dr. D. Steinhilber)
- Hans-Peter Zobel
Entwicklung von Acrylat-Nanopartikeln als Arzneistoffträger für Antisense-Oligonucleotide, Verlag Shaker, Aachen, ISBN 3-8265-3809-9 (1998)
- Helene Braun
Etablierung eines DNA-Transfersystems mit rekombinant hergestellten Polyoma VP1 Kapsiden, Verlag Shaker, Aachen, ISBN 3-8265-3907-9 (1998)
- Matthias Gilbert
Optimierung von Antisense-Oligonukleotiden- zwitterionische Nukleinsäuren und Trägersystemvariationen , Verlag Shaker, Aachen, ISBN 3-8265-7585-7 (2000)
- Eva Reisinger
Entwicklung retardierender peroraler Arzneiformen mit antitussiver Wirkung, Graz, Austria (2000)
- Susann Henke
Verwendung des viralen Polyoma-Hüllproteins VP1 zum Transfer von Nukleinsäuren in eukaryontische Zellen, Frankfurt a.M. (2001)
- Monika Junghans
Entwicklung und Vergleich nanopartikulärer und liposomaler Trägersysteme für Antisense-Oligonukleotide, Frankfurt a.M. (2001)
- Christof Geppel
Entwicklung thermosensitiver Doxorubicin-Stealth-Liposomen, Graz, Austria (2001)
- Anke Rohmann
Humanes Zellmodell zur Charakterisierung des viralen Polyoma-Strukturproteins VP1 zum Transfer von Antisense-Oligonukleotiden, Frankfurt a.M. (2002)
- Dirk Lochmann
Self Assembly von protaminbasierten Oligonukleotid-Nanopartikeln, Frankfurt a.M. (2004)
- Jörg Weyermann
Arzneistoff-Formulierung von Antisense-Oligonukleotiden gegen NMDA-Rezeptor-Expression, Frankfurt a.M. (2004)
- Birgit Deutschmann
Oberflächenmodifikation von Liposomen zum Targeting an Hepatozyten, Graz, Austria (2004)
- Georgia Leutgöb
Rasch zerfallende Arzneiformen zur Applikation in der Mundhöhle (2005)
- Margit Polsinger
Orale multiple unit Arzneiformen zur einmal täglichen Applikation (2005)
- Stefan Wegscheider
Entwicklung von neuen Arzneiformen für Somatropin (2007)
- Christiane Fürst
Charakterisierung biopolymerer Trägersysteme für Antisense-Oligonukleotide mittels Fluorescence Correlation Spectropscopy (2008)
- Karin Wernig
Protamin-Oligonucleotid-Nanopartikel als Drug Delivery System für Peptide und Proteine (2008)
- Daniela Reischl
RNA-Interferenz vermittelte Modulation der Proteinkinase D1-Expression in Gehinrtumoren: Kontrolle der Proliferation von Glioblastomzellen mittels protaminbasierter siRNA-Nanopartikel (2010)
Support - Sponsors
- BioNanoNet GmbH, Graz *
- (bm:bwk) Bundesministerium für Bildung, Wissenschaft und Kultur, Wien
- (DFG) Deutsche Forschungsgemeinschaft, Bonn
- Fresenius Kabi, Graz
- (FFG) Österreichische Forschungsförderungsgesellschaft, Wien *
- (FWF) Der Wissenschaftsfonds, Wien
- (JR) Joanneum Research, Land Steiermark, Graz *
- Lannacher Heilmittel GmbH, Lannach *
- µnadis GmbH, Leoben
- november AG, Erlangen
- Oridis Biomed, Graz
- Sandoz, Kundl
- Viatris Pharma, Wolfsberg
- Zukunftsfonds, Land Steiermark, Graz
* indicates currently active projects
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