Lehrstuhl für Biophysik am Gottfried Schatz Forschungszentrum

Medizinische Universität Graz

Nano-Lipo - Lipoproteins and Lipidic Nanoformulations

Ruth Prassl

Research Group:

Gunter Almer                        LBI-Lung Vascular Research
Daniela Frascione                 Regina Leber
Kerstin Gradauer                  Pritesh Jain
Karin Kornmüller                  Gebhard Schratter
Christian Mikl
Caroline Vonach

Our main research interests are directed towards the structure analysis of human plasma lipoproteins and the development of liposomal nanocarriers for targeted therapy and molecular diagnosis. Both themes are related to issues of membrane medicine and contribute to medical research in the field of chronic diseases.

Apolipoprotein B-100: A closer look at a cholesterol transporter

 

Lipoproteins are naturally occurring globular nanoparticles assigned with the function to supply tissues and cells with cholesterol and fat. Apolipoprotein B100 (apoB-100) is the only protein component of low density lipoprotein (LDL) triggering lipid transport and metabolism. Due to the size, dynamics and amphiphilic nature of apo-B100, the determination of its molecular structure remains to be a challenge.

 

Present  topics :

·          Molecular dynamics of atherogenic lipoproteins

·          Novel amphiphilic designer-peptides as solubilizing agents for apolipoprotein B-100

·          Membrane protein crystallization and macromolecular X-ray crystallography

Funding / Partner:

Austrian Science Fund, FWF / Med.Uni.Vienna, MFP-Laboratories

 

Selected References :

Mikl, C., Peters, J., Trapp, M., Kornmueller, K., Schneider, WJ., Prassl, R. (2011) Softness of Atherogenic Lipoproteins: A Comparison of Very Low Density Lipoprotein (VLDL) and Low Density Lipoprotein (LDL)Using Elastic Incoherent Neutron Scattering (EINS)  J. Am. Chem. Soc. 133, 13213-13215 (Selected as research highlight by ILL)

Prassl, R.,  Human low density lipoprotein (LDL): the mystery of  core lipid packing. (2011)  J. Lipid Res. 52 : 187-188.

Prassl, R. and Laggner P. (2009) Molecular Structure of Low Density Lipoprotein. Current Status and Future Challenge  Eur. Biophys. J. Biophys. Lett  38,2, 145 - 158

Prassl, R., M. Pregetter, H. Amenitsch, M. Kriechbaum, R. Schwarzenbacher, M.J. Chapman (2008) Low Density Lipoproteins as Circulating Fast Temperature Sensors PlosOne 3(12):e4079.

Johs, A., M. Hammel, I. Waldner, R.P.May, P. Laggner, and R. Prassl (2006) Modular structure of solubilised human apolipoprotein B-100: Low resolution model revealed by Small Angle Neutron Scattering, J.Biol.Chem. 281(28) : 19732-9

Liposomal nanocarriers for diagnostics, imaging and drug-delivery

 

The use of liposomes as pharmaceutical nanocarriers for treatment, diagnosis and monitoring of diseases has gained considerable interest within the last years. Meanwhile, liposomes have proven their pharmaceutical applicability as controlled release formulations, which can be  administered by different routes. Besides, liposomes are considered as promising targeted signal-emitter for non-invasive molecular imaging.  Advanced strategies in development of liposomes include polymer coating and surface functionalization with ligands or antibodies.

Present  topics :

·          Magnetoliposomes : Design, development and characterization of
           superparamagnetic ironoxide nanoparticle loaded liposomes for
           magnetic resonance imaging.

·          LIPOCEST : Development of a novel class of contrast agents for
           magnetic resonance imaging.

·          Targeted sterically stabilized liposomes for molecular imaging
           of atherosclerotic plaques.

·          Thioliposomes : Thiochitosan-coated liposomes with
           enhanced mucoadhesive properties for oral drug delivery.

·          Liposomes for miRNA delivery.

·          Liposomes as nanocarriers for pulmonary application via inhalation


Funding/ Partner :

Austrian Nano-Initiative, FFG / Consortium project "Nano-Health"(http://www.bionanonet.at/)
Government of Styria / Technical University of Graz
Ludwig Boltzmann Institute (LBI-) Lung Vascular Research (http://lvr.lbg.ac.at/)


Selected References :

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. (2011).gAdiponectin-coated nanoparticles for enhanced imaging of atherosclerotic plaques
International Journal of Nanomedicine 2011:6 1279 -1290.        

Almer, G., Saba-Lepek, M., Haj-Yahya, S., Rohde, E., Hofmeister, A., Strunk, D., Fröhlich, E., Prassl, R., Mangge, H. (2011) The globular domain of adiponectin-a promising target molecule for the detection of atherosclerotic lesions. Biologics: Targets and Therapy 2011: 5 95-105.

Helbok, A., Rangger, C., Saba-Lepek, M., Andreae, F., Radolf, T., Thurner, G., Prassl, R., Von Guggenberg, E., Decristoforo, C. (2011) Targeting properties of peptide modified radiolabelled liposomal nanoparticles. Nanomedicine: Nanotechnology, Biology and Medicine, May 20.

Stark, B., Pabst, G., Prassl, R. (2010) Long-term stability of sterically stabilized liposomes by freezing and freeze-drying: Effects of cryoprotectants on structure, European Journal of Pharmaceutical Sciences 41 : 546-555.

Helbok, A., C. Decristoforo, G. Dobrozemsky, C. Rangger, E. Diederen, B. Stark, R. Prassl, E. vonGuggenberg (2010) Radiolabelling of lipid based nanoparticles for diagnostics and therapeutic applications - a comparison using different radiometals. J Liposome Res. Sep;20(3):219-27.

Stark, B., F. Andreae, W. Mosgöller, M. Edetsberger, E. Gaubitzer, G. Köhler, and R. Prassl (2008) Liposomal Vasoactive Intestinal Peptide for Lung Application : Protection from Proteolytic Degradation. European Journal of Pharmaceutics and Biopharmaceutics. 70(1) :153-164.

Stark, B., P. Debbage, F. Andreae F., W. Mosgoeller, R. Prassl (2007) Association of vasoactive intestinal peptide with polymer-grafted liposomes : Structural aspects for pilmonary delivery. Biochim.Biophys.Acta 1768, 705-714.

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