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Supramolecular Aqueous Systems for Biomedical Applications

#3982


Supramolecular Nanostructured Aqueous Solutions and Gels of Low Concentrations as a Basis for Novel Pharmaceutical Formulations

Tech Area / Field

  • MED-RAD/Radiomedicine/Medicine
  • BIO-CHM/Biochemistry/Biotechnology
  • CHE-POL/Polymer Chemistry/Chemistry

Status
3 Approved without Funding

Registration date
11.08.2009

Leading Institute
State Educational Institution Tver State University, Russia, Tver reg., Tver

Supporting institutes

  • Research Center of Radiation Medicine and Burns, Armenia, Yerevan\nYerevan Institute "Plastpolymer", Armenia, Yerevan

Collaborators

  • Freie Universität Berlin / Institut für Chemie, Germany, Berlin\nUniversita di Pisa / Dipartamento di Patologia Sperimentale, Biotecnologie Medicine, Infettivologia ed Epidemiologia, Italy, Pisa\nUniversity of Washington / School of Medicine, USA, WA, Seattle\nUniversität Osnabrück / Institut für Chemie, Germany, Osnabrück

Project summary

Project Goals: The project is focused on obtaining novel supramolecular nanostructured aqueous systems (low concentrated solutions and gels) based on sulfur containing amino acids, silver nanoparticles and ions, modified polyvinyl alcohol to produce a matrix of pharmaceutical preparations regulating the cell pision and created for treatment of radiation injuries. In the frames of the project complex investigations of self-organization and gel-formation phenomena in aqueous multi-component systems will be performed, the role of the ions in the structure formation process will be studied; biological activity of these systems at different concentrations of the dispersed phase and their compatibility with a number of the biologically active substances will be defined. The results obtained will allow to create the novel efficient pharmaceutical formulations to treat localized radiation injuries.

Nowadays, one of the main options for treatment of malignant neoplasms is radiation therapy. Nevertheless, as a result of such a procedure radiation-associated lesions of skin, cell tissue and organs of pelvis minor are developed in about 30 % of the patients. Analyzing the existing methods of treatment of radiation-induced lesions one can state that their results are not-sufficient. By this reason there is an urgent need to create the novel pharmaceutical formulations and scientific approaches to improve dramatically the therapeutic interventions.

The authors of the project have discovered the unique system based on aqueous solutions of the simple amino acid L-cysteine and silver nitrate, which is able to form thixotropic hydrogels at ultra-low concentrations of the initial components (~0,01%). In the nature such systems are extremely rare and attract increased attention from scientific as well as practical points of view. Scientific significance of the project is explained by the opportunity to investigate the processes of self-organization and gel formation in supramolecular nanostructured aqueous systems based on the low molecular weight compounds. Practical importance is connected with the possibility to apply this system consisting from biologically active components as a matrix for producing highly efficient pharmaceutical formulations. It is established that the matrix itself has possessed not only antimicrobial properties, but also stimulated the cell pision. Additional introducing the biologically active compounds (water soluble polymers, medications, stem cells etc) into the system will increase efficiency of the created pharmaceutical preparations. Application of the novel formulations is particularly perspective in the treatment of patients with radiation injuries, because of the ionizing radiation mostly damages the cells during pision cycle.

One of the new strategies in development of pharmaceutical formulations is investigation of the effects of low and ultra-low doses (ULD) of biologically active substances and preparations traditionally applied at rather high concentrations. Increased attention to the creation of medicinal substances in ULD is paid by oncologists, as the main problem in chemotherapy of malignant neoplasms is high toxicity of anti-tumor compounds. It is established that some preparations at ultra-low doses (10-10-–10-20 M) have an ability to demonstrate the anti-tumor effect which is comparable with the activity of therapeutic doses of the preparations (10-2–10-3 М). Characteristic feature of the action of biologically active substances at ultra-low doses is non-monotonic, non-linear polymodal dependence “dose-effect”. The investigation of the self-organization processes in the nanostructured aqueous systems and the study of the properties of supramolecular compounds in the frames of the project will give some explanations of the effects of ULD.

It is supposed to study highly diluted systems based on the aqueous solutions of sulfur containing amino acids, silver ions and nanoparticles, electrolytes initiating the gelation, polyvinyl alcohol. Up to the present time, there are no approaches to explain the mechanism of gel-formation in such diluted compositions, in which concentration of the dissolved substances at definite conditions is <0,01 %. In particular, the role of metal ions and nanoparticles, necessity of presence of the sulfur atom in the amino acid molecule are not sufficiently revealed. Clarifying the elementary stages of the structure formation in such systems by the help of dynamic light scattering (DLS), FTIR and UV-vis spectroscopy, electron microscopy, rheokinetics, quantum-mechanical calculations and molecular simulations is planned in the work. Definite attention will be devoted to the influence on the gelation of the additions changing ratio of the free and bound ions, acidity of the medium. It is supposed to perform also the search of other ions and amino acids, which are able to structurize aqueous solution and to form gels that allows us to understand better the nature of the studied phenomenon. Such a complex approach will allow not only to elucidate the dynamics of self-organization processes, but also to utilize the developed principles for targeted searching and creating the novel hydrogels for biomedical applications.

To evaluate the biological activity of the developed compositions the study of the influence of the systems on the lipid peroxidation (LPO) in blood erythrocytes and on the chromosome apparatus of blood lymphocytes in a wide range of concentrations including low and ULD, in vitro, is planned. Investigation of the cytogenetic status of a somatic cell under the action of the studied systems will allow to estimate their biological effect. The efficiency of the developed compositions for treatment of various radiation injuries will be examined in experiments, optimal regimen and schemes for administration of the preparations will be found.

In the proposed project the results obtained earlier by the project’s participants will be used. Since many years the group of the authors has carried out the experimental investigations of the gel-formation process in various polymeric systems. Combination of the experimental techniques suggested for the project’s implementation creates the real conditions for its successful realization. As a result of the project’s activity it is expected to obtain formulations based on silver ions and nanoparticles, amino acid and PVA to treat complicated forms of radiation injuries of different locations.

The project corresponds to ISTC goals, as weapon scientists and specialists from three research organizations of the former USSR will be engaged in its implementation.

The role of foreign collaborators in the frames of the project will include joint discussions and information exchange during the project’s realization.


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