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I. Head of Research Group:
II. Senior Scientist:
in collaboration with
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 (2004 - 2009):
| 29. |
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 (2009) in press |
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| 28. |
Roblegg E.,* Sinner F. and Zimmer A.
Health Risks of Nanotechnology
Euro Nano Tox Letters (2009) in press. |
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| 27. |
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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| 26. |
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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| 25. |
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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| 24. |
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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| 23. |
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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| 22. |
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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| 21. |
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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| 20. |
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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| 19. |
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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| 18. |
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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| 17. |
Kerkmann M., Lochmann D., Weyermann J., Marschner A., Poeck H., Wagner M., Zimmer A., Endres S., Hartmann G*.
Immunostimulatory properties of CpG-oligonucleotides are enhanced by the use of protamine nanoparticles
Oligonucleotides 4 (2006) 313-322. |
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| 16. |
Mayer G., Vogel V., Weyermann J., Lochmann D., van den Broek J. A., Tziatzios C., Haase W., Wouters D., Schubert U. S., Zimmer A., Kreuter J., and Schubert D.*,
Oligonucleotide-protamine-albumin nanoparticles: Protamine sulfate causes drastic size reduction
J Control Release 106 (2005) 181-187. |
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| 15. |
Junghans M., Loitsch S.M., Steiniger S., Kreuter J., and Zimmer A.*,
Cationic lipid–protamine–DNA (LPD) complexes for delivery of antisense c-myc oligonucleotides
Eur J Pharm Biopharm (2005) 287-294. |
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| 14. |
Michaelis, M., Zimmer, A., Handjou, N., Cinatl, J., and Cinatl, J., Jr.*
Increased systemic efficacy of aphidicolin encapsulated in liposomes.
Oncol Rep 13 (2005) 157-160. |
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| 13. |
Weyermann, J., Lochmann, D., Georgens, C., and Zimmer, A.*,
Albumin-protamine-oligonucleotide-nanoparticles as a new antisense delivery system. Part 2: cellular uptake and effect,
Eur J Pharm Biopharm 59 (2005) 431-438. |
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| 12. |
Lochmann, D., Weyermann, J., Georgens, C., Prassl, R., and Zimmer, A.*,
Albumin-protamine-oligonucleotide nanoparticles as a new antisense delivery system. Part 1: Physicochemical characterization,
Eur J Pharm Biopharm 59 (2005) 419-429. |
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| 11. |
Vogel, V., Lochmann, D., Weyermann, J., Mayer, G., Tziatzios, C., van den Broek, J. A., Haase, W., Wouters, D., Schubert, U. S., Kreuter, J.*, Zimmer, A., and Schubert, D.,
Oligonucleotide-protamine-albumin nanoparticles: preparation, physical properties, and intracellular distribution,
J Control Release 103 (2005) 99-111. |
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| 10. |
Georgens, C., Weyermann, J., and Zimmer, A.*,
Recombinant virus like particles as drug delivery system,
Curr Pharm Biotechnol 6 (2005) 49-55. |
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| 9. |
Weyermann, J., Lochmann, D., and Zimmer, A.*,
A practical note on the use of cytotoxicity assays,
Int J Pharm 288 (2005) 369-376. |
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| 8. |
Weyermann, J., Lochmann, D., and Zimmer, A.*,
Comparison of antisense oligonucleotide drug delivery systems,
J Control Release 100 (2004) 411-423. |
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| 7. |
Lochmann, D., Stadlhofer, S., Weyermann, J., and Zimmer, A.*,
New protamine quantification method in microtiter plates using o-phthaldialdehyde/N-acetyl-L-cysteine reagent,
Int J Pharm 283 (2004) 11-17. |
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| 6. |
Lochmann, D., Jauk, E., and Zimmer, A.*,
Drug delivery of oligonucleotides by peptides,
Eur J Pharm Biopharm 58 (2004) 237-251. |
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| 5. |
Lochmann, D., Weyermann, J., Kreuter, J., Vogel, V., Schubert, D., Dinauer, N., Von Briesen, H., and Zimmer, A.*,
Physicochemical characterization of protamine-phosphorothioate nanoparticles,
J Microencapsulation 21 (2004) 625-641. |
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| 4. |
Budai, M., Szabó, Z.*, Szögyi, M., Gróf, P., and Zimmer, A.,
Studies on molecular interactions between nalidixic acid and liposomes,
Int J Pharm 279 (2004) 67-79. |
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| 3. |
Weyermann, J., Lochmann, D., Georgens, C., Rais, I., Kreuter, J., Karas, M., Wolkenhauer, M., and Zimmer, A*.
Physicochemical characterisation of cationic polybutylcyanoacrylate-nanoparticles by fluorescence correlation spectroscopy.,
Eur J Pharm Biopharm 58 (2004) 25-35. |
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| 2. |
Dinauer, N., Bouazzaoui, A., Von Briesen, H.*, Lochmann, D., Kreuter, J., Demirhan, I., Chandra, A., and Zimmer, A.,
Intracellular tracking of protamine/antisense oligonucleotide nanoparticles and their inhibitory effect on HIV-1 transactivation,
J Control Release 96 (2004) 497-507. |
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| 1. |
Rohmann, A., Lochmann, D., Weyermann, J., Bertling, W. M., Dingermann, T., and Zimmer, A*.
Rapid screening method for antisense oligonucleotides against human growth factor receptor p185(erbB-2),
Oligonucleotides 14 (2004) 1-9. |
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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)
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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