Thesis supervisor: Tibor Páli
belső konzulens: Teruaki Koto
Web address (URL): http://membrane.brc.hu Location of studies (in Hungarian): Institute of Biophysics BRC, ELKH Abbreviation of location of studies: SZBK
Description of the research topic:
There is a huge medical demand on efficient liposome drug delivery formulas. However, the most commonly used phospholipid liposomes have several disadvantages such as broad size distribution, sensitivity to sterilisation, etc. Very promising alternative systems are catanionic liposomes formed by a mix of cationic and anionic amphiphiles. The spontaneous formation, higher colloidal stability and versatility in charge and size have made catanionic liposomes attractive novel candidates for drug delivery. We plan to collaborate with Prof. Musti J. Swamy (School of Chemistry, Uni. Hyderabad, India) on the topic. They have a great expertise on handling lipid and membrane systems, including catanionic liposomes, and their analysis using calorimetric and X-ray techniques. His team is studying the interaction of amino acid based cationic surfactants with anionic surfactants. Importantly, they have reported the preparation and characterisation of catanionic liposomes made up of alkyl esters of glycine, alanine and sarcosine (as the anionic surfactant), and sodium dodecyl sulphate. Studies carried out at different pH indicated that liposomes made up of selected catanionic complexes are labile under basic pH, suggesting that they can potentially be used for targeting therapeutic agents to organs/tissues that are inherently at basic pH, such as colon. Since we have expertise on membrane biophysics based on spin-labeling and spin-trapping EPR and other spectroscopic techniques, our collaboration will provide an optimal combination of complementary expertise and research infrastructure to examine liposomes and biomembranes. The research programme is as follows:
• We will investigate the interaction of selected anti-cancer drugs and other therapeutic agents with catanionic liposomes using spin-label electron paramagnetic resonance (EPR) spectroscopy.
• The stability of the liposome/drug combinations will be also tested in the presence of biological fluids (e.g., serum, saliva, etc).
• Based on the results obtained, specific liposome formulas will be selected for further studies with experimental animal models.
Selected references
Pali, T. & Horvath, L. I. (1989) Restricted lateral diffusion of acidic lipids in phospholipid vesicles aggregated by myelin basic protein. Biochimica et Biophysica Acta 984, 128-134.
Pali, T., Bartucci, R., Horvath, L. I. & Marsh, D. (1993) Kinetics and dynamics of annealing during sub-gel phase formation in phospholipid bilayers. A saturation transfer electron spin resonance study. Biophysical Journal 64, 1781-1788.
Nedeianu, S., Pali, T. & Marsh, D. (2004) Membrane penetration of nitric oxide and its donor S-nitroso-N-acetylpenicillamine: a spin-label electron paramagnetic resonance spectroscopic study. Biochimica et Biophysica Acta - Biomembranes 1661, 135-143.
Tarafdar, P.K., Reddy, S.T., Swamy, M.J. (2010) A Base-Triggerable Catanionic Mixed Lipid System: Isothermal Titration Calorimetric and Single-Crystal X-ray Diffraction Studies. J. Phys. Chem. B. 114, 13710-13717.
Sivaramakrishna, D., Swamy, M.J. (2015) Self-assembly, Supramolecular Organization and Phase Behavior of L-Alanine Alkyl Esters (n = 9-18) and Characterization of Equimolar L-Alanine Lauryl Ester/Lauryl Sulphate Catanionic Complex. Langmuir 31, 9546-9556.
Reddy, S.T., Sivaramakrishna, D., Swamy, M.J. (2017) Biophysical Characterization of Lauryl Glycinate-Dodecyl Sulfate Equimolar Complex: A Base-Triggerable Catanionic Liposomal System. Colloids Surfaces A: Physicochem. Eng. Aspects 516, 139-146.
Páli, T. & Kóta, Z. (2019) Studying Lipid-Protein Interactions with Electron Paramagnetic Resonance Spectroscopy of Spin-Labeled Lipids. Methods Mol Biol 2019, 2013, 529-561.
Required language skills: English Number of students who can be accepted: 2
Deadline for application: 2022-04-06
2024. IV. 17. ODT ülés Az ODT következő ülésére 2024. június 14-én, pénteken 10.00 órakor kerül sor a Semmelweis Egyetem Szenátusi termében (Bp. Üllői út 26. I. emelet).
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