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Projects / Programmes source: ARIS

Formulation and characterization of fuzogenic colloidal nanoparticles for efficient drug delivery into cells

Research activity

Code Science Field Subfield
7.00.00  Interdisciplinary research     

Code Science Field
B120  Biomedical sciences  Molecular biophysics 
Keywords
Colloidal nanoparticles, liposomes, alkylphospholipids, chemotherapy, cancer, targeted drug delivery, cell membranes, membrane domains, EPR, spin probes, fluorescence spectro-microsopy
Evaluation (rules)
source: COBISS
Researchers (11)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  23566  PhD Zrinka Abramović  Physics  Researcher  2008  42 
2.  20208  PhD Zoran Arsov  Biotechnology  Researcher  2008 - 2011  135 
3.  21546  PhD Tilen Koklič  Physics  Researcher  2008 - 2011  138 
4.  30633  Sandra Kure    Technical associate  2008 - 2010  16 
5.  33075  Alma Mehle    Technical associate  2011  14 
6.  23419  PhD Janez Mravljak  Pharmacy  Researcher  2008 - 2011  201 
7.  08742  Marjanca Nemec    Technical associate  2008 - 2009  81 
8.  03070  PhD Slavko Pečar  Pharmacy  Researcher  2008 - 2011  415 
9.  01119  PhD Marjeta Šentjurc  Biochemistry and molecular biology  Head  2008 - 2011  511 
10.  18273  PhD Janez Štrancar  Physics  Researcher  2008 - 2011  372 
11.  30871  PhD Maja Zorc  Physics  Junior researcher  2009 - 2011  57 
Organisations (2)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0106  Jožef Stefan Institute  Ljubljana  5051606000  90,600 
2.  0787  University of Ljubljana, Faculty of Pharmacy  Ljubljana  1626973  17,462 
Abstract
The main goal of the proposed project is to select appropriate liposomal formulation for efficient delivery of cancerostatic alkyl phospholipids (APL) into cells. APLs are new type of anticancer drugs, which do not target DNA, but exert their action at the cell membrane. Because of their gastrointestinal toxicity and hemolytic activity it is necessary to find a formulation that should allow an optimal balance between cancerostatic efficiency and undesirable side effects. Liposomal formulation of APL seems promising. We propose a hypothesis that appropriate composition of liposomes with APL will enable these liposomes to fuse with cells, what will improve accumulation of APL in plasma membrane and in this way increase their cytotoxicity. In order to test our hypothesis APL liposomes of different composition will be prepared and the influence of membrane domain structure of liposomes and cells on their interaction and on the cellular uptake of APL will be investigated. Membrane domain structure of liposomes and cells will be studied by electron paramagnetic resonance (EPR) method in conjunction with the computer program for EPR spectra line shape simulation, which enables to obtain information about the dynamic characteristics of membrane domains. For studying cellular uptake and the mechanism of liposome cell interaction spin labeled APL or hydrophilic labels will be used and their transport into the cells investigated. EPR spectroscopy will be combined with fluorescence spectro-microscopy, while cytotoxicity and stability of APL liposomes will be measured in dr. Zeisig’s laboratory in Berlin. Results proposed in this project will contribute to better understanding of mechanisms of action of alkyl phospholipids, which is important for their further application as a new type of chemotherapeutic drugs and to better understanding of the mechanisms involved in fusion of model and real cell membranes what is of prime interest not only for delivery of chemotherapeutic drugs but also for the delivery of plasmid DNA into the cells
Significance for science
Results will contribute to: • better understanding of mechanisms of interaction of akylphospholipids (APL) with cells • a development of APL liposomes for treatment of tumors with enhanced cancerostatic efficiency and less undesirable side effects; • better understanding of membrane domain structure in the process of fusion of real and model membranes • better understanding of the role of membrane domain structure in the process of transcytosis • a development of liposomes for the transport of drug via blood-brain barrier into the brain. • a development of new drugs and pharmaceutical formulations.
Significance for the country
This investigation could be important for pharmaceutical industry, which is one of most prosperous fields in our country. Within this project PhD students and young doctors of science are educated in different fields of life sciences. Therefore they will be able to contribute with their knowledge to faster economic growth in different fields of industry and especially in the pharmaceutic and food industry.
Most important scientific results Annual report 2008, 2009, final report, complete report on dLib.si
Most important socioeconomically and culturally relevant results Annual report 2008, 2009, final report, complete report on dLib.si
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