Loading...
Projects / Programmes source: ARIS

Nanoparticle-macromolecule complexes for use in formulation of biological drugs

Research activity

Code Science Field Subfield
2.04.00  Engineering sciences and technologies  Materials science and technology   

Code Science Field
P360  Natural sciences and mathematics  Inorganic chemistry 
P352  Natural sciences and mathematics  Surface and boundary layery chemistry 
T155  Technological sciences  Coatings and surface treatment 
T150  Technological sciences  Material technology 
T152  Technological sciences  Composite materials 
Keywords
Nanomedicine, targeted delivery, controlled release, nanoparticles, protein folding, mactomolecular interactions
Evaluation (rules)
source: COBISS
Researchers (14)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  11517  PhD Marjan Bele  Materials science and technology  Researcher  2008 - 2011  544 
2.  18325  PhD Simon Caserman  Biochemistry and molecular biology  Researcher  2008 - 2011  107 
3.  19165  PhD Marjetka Conradi  Physics  Researcher  2008 - 2011  158 
4.  06108  PhD Vladimira Gaberc-Porekar  Biotechnology  Researcher  2008 - 2011  220 
5.  00582  PhD Miran Gaberšček  Materials science and technology  Researcher  2008 - 2011  899 
6.  29487  PhD Aljaž Godec  Physics  Junior researcher  2008 - 2011  80 
7.  26055  PhD Gorazd Hribar  Biochemistry and molecular biology  Junior researcher  2008 - 2009  49 
8.  10180  PhD Janko Jamnik  Materials science and technology  Head  2008 - 2011  337 
9.  27920  Gregor Kapun  Chemistry  Researcher  2008 - 2009  102 
10.  16408  PhD Klemen Kočevar  Physics  Researcher  2008 - 2011  63 
11.  24976  PhD Milena Martins  Materials science and technology  Technical associate  2008 - 2011  102 
12.  09089  PhD Igor Muševič  Physics  Researcher  2008 - 2011  750 
13.  18289  PhD Peter Svete  Chemistry  Researcher  2008 - 2011  31 
14.  22137  Bernarda Urankar  Educational studies  Researcher  2009 - 2011  26 
Organisations (4)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0104  National Institute of Chemistry  Ljubljana  5051592000  20,869 
2.  0106  Jožef Stefan Institute  Ljubljana  5051606000  90,038 
3.  0206  Institute of Metals and Technology  Ljubljana  5051622000  5,941 
4.  0258  Lek Pharmaceutical Company d.d.  Ljubljana  1732811  8,400 
Abstract
Nanomedicine is a new scientific field that has immensely evolved during last 5 years. The forefronts in nanomedicine are the delivery and targeting of pharmaceutical, therapeutic, and diagnostic agents. A precisely targeted drug delivery to the diseased cells only would be regarded a major breakthrough having impact in various directions: the therapetic efficiency would increase, the in-vivo drug degradation would decrease, the drug consumption and price would decrease, the side effects would be minimized. The basic idea in this project is to develop a new generation of materials for targeted drug delivery based on nanoparticles. The therapeutic drug will not be enclosed into particle interior as proposed in most present strategies but rather attached onto the outer surface of a nanoparticulate substrate. The basic configuration of the proposed delivery system will be the following: the core will consist of a biodegradable nanoparticle (not necesserically spherical) with a typical dimension smaller than ca. 150-200 nm. The surface of nanoparticle will be modified in such a way to enable reversible bonding of therapeutic (protein) molecule. The modification will be carried out by either forming an appropriate (in)organic monolayer or using appropriate linkers. In the latter case, the bonding between nanoparticle surface and linker will be irreversible while that between the linker and drug molecule will be reversible. The adsorbed drug molecules could simultaneously serve as therapeutic and targeting agents; in the case they are different, appropriate modifications of the basic concepts are envisaged. The project will encompas materials synthesis, full materials characterization and theoretical modeling.
Significance for science
Functionalization of nanoparticles with selected materials or molecules is a current hot topic in materials science, especially in the field of materials for pharmaceutical applications.Most importantly, the activivity of such a molecule could be (completely) restored after decoupling from the particle. This final result would certainly present an important breakthrough towards more controlled action of various biological drugs. Improved understanding of the underlying mechanism in such controlled experiments helps understand certain processes taking place in the living organisms. Protein decorated nanoparticles can serve as efficient triggers of immune response, leading to antibody formation and so to successful immunization. TNF-? is of special interest as a model protein for preparation of medicines, which trigger the immune response, because we have to alter its high systemic toxicity as well as its short half-life time (20-30 minutes), which make the protein itself inappropriate for immunization. Protein nanoparticles composed of many molecules are expected to be more immunogenic and also less toxic, due to a significantly diminished number of accessible receptor binding sites resulting from binding of the proteins to the surface of the nanoparticles, which is supposed to lead to temporary changes of conformation. An enhanced formation of antibodies against TNF-? could serve as a basis for developing new drugs for treatment of chronic diseases associated with pathogenically elevated levels of TNF-?, such as rheumatoid arthritis, Crohn’s disease, psoriasis, etc. Due to the fact that anticytokine autoantibodies were found not only in patients with chronic inflammatory diseases, but also in healthy individuals, the principle of active immunotherapy seems to be a very promising approach. In comparison with present passive immunotherapies, involving high concentrations of anti-TNF-? antibodies or TNF receptors, it has several advantages, including simplicity, lower costs and better patient compliance. This approach might also be useful for numerous other proteins that are inappropriate for direct immunization.
Significance for the country
The project has been highly relevant for both the economy and the society because it has dealt with improvement of drug efficiency. In perspective, a successful continuation of the basic project results can have impact on better treatment of diseases (including those that cannot be treated appropiately at present), on lowering the drug prices and reduction/minimization of side effects. It is clear that such drugs will be more than welcome by end-users (in our case Lek, d.d.).
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
Views history
Favourite