Projects / Programmes
Nanoparticle-macromolecule complexes for use in formulation of biological drugs
| 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 |
Nanomedicine, targeted delivery, controlled release, nanoparticles, protein folding, mactomolecular interactions
Researchers (14)
Organisations (4)
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
