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Projects / Programmes source: ARRS

Načrtovanje in predklinični razvoj novih zdravilnih učinkovin (Slovene)

Periods
Research activity

Code Science Field Subfield
1.09.00  Natural sciences and mathematics  Pharmacy   

Code Science Field
3.01  Medical and Health Sciences  Basic medicine 
Evaluation (rules)
source: COBISS
Researchers (18)
no. Code Name and surname Research area Role Period No. of publications
1.  33694  PhD Dejan Arzenšek  Physics    2011 - 2013 
2.  21437  PhD Tadej Čepeljnik  Biotechnology  Researcher  2009 - 2013  51 
3.  05088  PhD Manica Černe  Veterinarian medicine  Researcher  2009 - 2013  106 
4.  30615  PhD Katarina Fidler  Biochemistry and molecular biology  Researcher  2011 - 2013  14 
5.  23940  PhD Boštjan Japelj  Physics  Researcher  2009 - 2013  37 
6.  16171  PhD Simona Jevševar  Biotechnology  Researcher  2009 - 2013  51 
7.  22679  PhD Maja Kenig  Pharmacy  Researcher  2009 - 2013  21 
8.  30674  PhD Menči Kunstelj  Pharmacy  Technician  2010 - 2013  18 
9.  23686  PhD Mateja Kusterle  Biotechnology  Researcher  2009 - 2013 
10.  18355  PhD Drago Kuzman  Pharmacy  Researcher  2009 - 2013  62 
11.  24465  PhD Luka Peternel  Cardiovascular system  Researcher  2009 - 2013  49 
12.  20681  PhD Barbara Podobnik  Pharmacy  Researcher  2009 - 2013  62 
13.  19366  PhD Aleš Premzl  Pharmacy  Researcher  2009 - 2013  81 
14.  24289  PhD Matej Seliškar  Biochemistry and molecular biology  Researcher  2009 - 2013  25 
15.  24925  PhD Vanja Smilović  Biotechnology  Researcher  2010 - 2013  13 
16.  26075  PhD Špela Škrajnar  Veterinarian medicine  Researcher  2009 - 2013  19 
17.  19171  PhD Igor Kristian Štern  Biotechnology  Researcher  2009 - 2013  31 
18.  01878  PhD Uroš Urleb  Pharmacy  Principal Researcher  2009 - 2013  377 
Organisations (1)
no. Code Research organisation City Registration number No. of publications
1.  0258  Lek Pharmaceutical Company d.d.  Ljubljana  1732811  10,073 
Significance for science
Genomic and proteomic research is rapidly unveiling the molecular basis of many diseases and consequently also many new candidates for therapeutics, which are complex biologics. Although their characteristics allow excellent therapeutic effect, their fragile and sensitive structure and the body’s ability to rapidly remove them from the bloodstream severely limit their administration. In addition to prolonged biological availability protein modification enables improvement of protein characteristics to such extent that not only significantly less frequent administration is possible, but also alternative drug delivery systems could be used. In the research area for the preparation of an improved version of the long acting hG-CSF to treat neutropenia, we contributed several PEGylated hG-CSF conjugates with improved properties, which may contribute to the future development of biobetter drug variants (also in combination with our proprietary biodegradable PEG reagents). Accumulation of long non-degradable PEG chains is recognized as one of the key weaknesses of PEGylation technology, thus biodegradable PEG reagents represent important development step towards the improved safety of PEGylated biopharmaceutics as it would allow the administration of higher doses and their use in chronic diseases treatments, where the use of PEGylated proteins is nowadays very limited. Since PEGylation leads to reduced biological activity of protein molecules in vitro it can be used for reducing of possible toxicity of some molecules. We tried to show and take all possible advantages of PEGylation, such as prolonged elimination half-life and reduced systemic toxicity of molecule with preserved biological activity, on our key model molecule TNF-alpha. We prepared appropriately PEGylated TNF-alpha analogs which show potential for use in the systemic anticancer therapy representing good basis for further research and development in this scientific field. Modification or diminishing of biological activity of TNF-alpha by protein modification was explored in order to prepare candidates for inhibition of native TNF-alpha exhibiting less side effects than currently available antiTNF therapeutics for treatment of diseases such as rheumatoid arthritis, Crohn's disease and psoriasis. Our approach and results of the program show wider applicability of PEGylation technology, not limited only to half-life extension of proteins in the body. Poor absorption of protein from gastrointestinal tract is a consequence of the protein’s structural characteristics, being physically, chemically and proteolyticaly unstable in the harsh conditions in the gastrointestinal tract (GIT), and too large and too hydrophilic to penetrate through the intestinal epithelium. Hence protein based medicines are administrated invasively, patient unfriendly by injection. Although an intensive research is going on world-wide in the field of peroral delivery of proteins and this is unambiguous unmet medical need, biopharmaceutics in such form is not yet available for the patients. Although some candidate molecules are in various stages of clinical trials, it is still a very big challenge and will mean an important breakthrough for the science. Although economically viable peroral delivery of proteins at the current price of biopharmaceutics seems to be a very distant goal, we have managed to demonstrate in our research that the protection of the protein in nanoparticles, conjugation for increased mucopermeability and enhanced gastrointestinal absorption result in an increase in the bioavailability of proteins. These results represent an important contribution to science in the development field of patient-friendly delivery systems for biopharmaceutics.
Significance for the country
Direct importance for the economy and society Maintenance of R&D capacities in pharmaceutical industry is a national priority stated in all strategic documents of the Republic of Slovenia, where pharmaceutical industry is traditionally one of the most developed and socially economically important industries. The pharmaceutical company Lek has recognized the potential added value of research in the field of anticancer drugs and directed part of R&D funds into research connected to the establishment of the new platforms for their development. Successful execution of the proposed program means establishment of a complex scientific and technological platform for the preparation of protein based active pharmaceutical ingredients by applying post-production protein modification technology (i.e. preparation of conjugates with different polymers as well as their analytical characterization) and intensification of research and further enhancement of the advanced industrial research within Lek. All this will importantly contribute to strengthening of role of center for development and manufacturing of biopharmaceutics within the Sandoz/Novartis bringing long-term competitive advantage and ensure high-tech jobs in Slovenia. The later is especially important for Slovenia as we lag behind more developed countries in the field of technological enterprises with own research. Realization of program during 2009-2013 is a very good basis for the approved program proposal continuation focused on new molecules, antibody drug conjugates (ADC) for targeted anticancer therapy. If further research supported also by approved program continuation leads to discovery of improved new forms of ADCs, we will thereby succeed in offering Slovenia an original drug. In view of the ever higher importance of treatment of cancer, this would be an extraordinary research, moral and material success. Since R&D in Lek are goal-orientated and supported with international cooperation, the possibilities for a successful completion of development of an improved substance at least to the phase of clinical candidate are real. Regarding involvement of the proposed research into trends of the global pharmacy this is an area with very intensive partnerships between pharmaceutical multinational corporations and highly innovative groups (academic and small biotech companies). Importance for the development of the profession and engineering practice. Research program group within an industry is a guaranty for applicable science. It means an increase of employment for top Slovenian researchers and thus justifies significant national investments in PhD education programs. At the same it is the driving force for academia-industry consortiums and collaborations, already proven and expressed in our work in the past. In addition the expert knowledge and skills gained during execution of the program has a great potential for high-tech spin-off companies. New knowledge and introducing of new technological platforms are vitally important for further development of pharmacy and biotechnology in Slovenia. Indirect importance for the society Publication in the international scientific journals and the patenting of the results will contribute to the strengthening of national identity. At the same time the efforts of the research group on the development of anticancer drugs will certainly contribute to the reputation and recognition of our researchers within an international scientific community.
Most important scientific results Annual report 2009, 2010, 2011, 2012, final report, complete report on dLib.si
Most important socioeconomically and culturally relevant results Annual report 2009, 2010, 2011, 2012, final report, complete report on dLib.si
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