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Polymer Composites for Skin Burns and Wounds Treating

#3595


Development of Composite Polymer Coatings Based on Natural and Synthetic Polymers, Containing Complexes of Porphyrins with Amphiphilic Polymers, for Photodynamic Therapy of Skin Burns and Festering Wounds

Tech Area / Field

  • MED-DRG/Drug Discovery/Medicine
  • BIO-MIB/Microbiology/Biotechnology
  • MED-DID/Diagnostics & Devices/Medicine
  • CHE-POL/Polymer Chemistry/Chemistry
  • CHE-RAD/Photo and Radiation Chemistry/Chemistry

Status
3 Approved without Funding

Registration date
21.08.2006

Leading Institute
Russian Academy of Sciences / Semenov Institute of Chemical Physics, Russia, Moscow

Supporting institutes

  • NIIIT (Pulse Techniques), Russia, Moscow\nKarpov Institute of Physical Chemistry, Russia, Moscow\nState Scientific Center of Laser Medicine, Russia, Moscow

Collaborators

  • Harvard Medical School / Wellman Center for Photomedicine, USA, MA, Boston\nWayne State University / School of Medicine, USA, MI, Wayne\nLancaster University / Department of Physics, UK, Lancaster\nNational Institute of Health, Italy, Rome

Project summary

Burns and other skin damages are widespread traumatic injuries. As the increasing danger of natural disasters, terrorist attacks, and industrial catastrophes leads to a growing number of such injuries and festering wounds, the problem of prompt therapeutic treatment of skin surface damages, burns, festering wounds becomes of current concern.

The modern practice of conservative treatment of festering wounds and complicated burns assumes the use of antiseptics, antibiotics, ferments or their compositions. However, these medications do not enough effect and, besides, have no necessary antimicrobial activity because the structure of the agent of purulent infections has changed by now.

Recently, photodynamic therapy (PDT) has been used for treatment of festering wounds and trophic ulcers. The method was developed to treat malignant tumors. It is based on the use of porphyrin photosensitizers (PPS) under enlightening conditions. An important advantage of PDT is its ability to affect bacterial cultures that are resistant to antibiotics. However, the use of only PDT does not usually guarantee a stable antiseptic effect and can not prevent an external infection of wounds and burns. In addition, its use is restricted by PPS phototoxicity, which holds up for a long time (up to two weeks).

The study carried out in the ISTC Project 2280 resulted in a PDT method using a local introduction of PpS immobilized on amphiphilic polymer (AP) carrier. It was shown that the use of PPS-AP complexes enables significantly, by an order of magnitude, increase the PDT efficiency, significantly decrease thePPS concentrations used.

The goal of given Project is a development of complex method of treating burns and wounds on the base of combination of PDT with bactericidal effects that can be achieved by immobilization of PPS on AP having their own bactericidal action. This method would enable to carry out the primary treatment of wounds and burns to prevent their further infection, using a simple autonomous apparatus for PPS photoexcitation under emergency conditions. Stationary medical setups using this method could provide a complex healthy effect on wound and burn treatment at all its basic stages: inflammation, regeneration and epithelization.

It is important to note that a not expensive mobile autonomous installation will be developed to carry out the primary treatment of wounds and burns of various localizations in field emergency conditions basing on a new method.

Research team experience. The Project team members at ICP and RICP acquired a wealth of experience in immobilization of porphyrin photosensitizers on synthetic and natural polymer carriers, which represent effective photocatalytic systems. [A.B.Solovieva, E.A.Lukashova, A.V.Vorobiev, and S.F.Timashev. Polymer sulfofluoride films as carriers for metalloporphyrin catalysts, Reactive Polymers, 16, (1991-1992) pp. 9-17; A.B.Solovieva, S.L.Kotova, S.A.Zavijalov, T.N.Rumantseva, N.N.Glagolev, and S.F.Timashev, Porphyrins Immobilized on Polymeric Supports as Sensitizers of the Photogeneration of Singlet Oxygen. Russian Journal of Physical Chemisry, Vol. 74, Suppl.1, 2000, pp. S92-S97; A.B.Solovieva, S.F.Timashev. Catalyst systems based on immobilized porphyrins and metalloporphyrins, Russian Chemical Reviews, Vol. 72 (11), 2003, pp. 965-984]. This will enable to obtain the optimal effective, stable, gas-permeable samples.

A wealth of practical experience of Project participants at SSCLM in studying the effect of directed photodynamic treatment on festering wounds in vitro and in vivo and also in practical treatment of patients with festering wounds [Stranadko E.F., Tolstykh P.I., Korablev U.M., Shekhter A.B. Experimental investigation of PDT effect on the healing of festering wounds. “Laser Medicine, 2001, v.5, N2, 8-13] will enable to carry out successfully the tests of the method of treatment of burns and festering wounds on laboratory animals and conduct the clinic tests.

The Project participants at RIPT acquired a lot of successful experience in designing and construction of precision devices for studying physical and photochemical processes. This will provide development of an unique mobile installation for carrying out PDT in both hospital and field conditions.

A planned activity will be three years.

By the end of the first year, it is planned to obtain:

  • Samples of the most effective PPS-AP complexes obtained.
  • Results of investigations of PDT efficiency on cells of various infection types using obtained PPS-AP complexes.
  • Data of microscopic investigations of the cell structures subject to PDT in the presence of PPS-AP complexes.
  • Model laboratory installation for PDT of surface wounds and burns.

By the end of the second year, it is planned to obtain:
  • Samples of polymer compositions on the base of synthetic biodegradable polymers containing PPS-AP complexes.
  • Results of the tests in model conditions (liquid phase) of the systems PPS-AP-biodegradable polymers on photodestruction, strength of PPS fastering and PPS lifetime.
  • Results of tests of the systems PPS-AP-biodegradable membranes on efficiency of effects on wound processes at various stages (on laboratory animals).
  • Technique for identification of wound or burn surface state (inflammation, regeneration, epithelization) by the characteristics of own and reflected optic and IR light.

By the end of third year, it is planned to obtain:
  • Samples of natural polymer materials containing PPS-AP complexes.
  • Results of the tests of PPS-AP complexes immobilized on natural materials on cell cultures.
  • Results of tests of model laboratory installation for PDT of wounds of various localization for different PDT regimes using all the types of PPS-AP-polymer films systems (on laboratory animals).
  • Laboratory version of portable inst5allation for PDT of wound and burn surface.
  • Recommendations on production and use of installations for treatment of festering wounds and burns using PDT and bactericidal treatment using porphyrin containing composite polymer materials.
  • Results of approbation of the portable installation in clinic conditions.

Thus due to the Project the fundamentally new drags will be created for combined wounds and burns treatment on base of PDT method and bactericidal polymer films. The developed polymer films containing PPS-AP complexes will be stable during storage and use. They will be proper for therapy of (complicated) burns, light wounds, festering wounds and trophic ulcers. A portable installation will be developed for local PDT treatment.

The obtained results will be of great scientific value to understand a mechanism of interaction of cells with porphyrin containing photosensitizers. They can have a commercial value for production of medicals for burns, trophic ulcers and wounds treatment and installations for treatment in extraordinary conditions.

The proposed technical approach takes into account the complexity and interdisciplinary character of the problem. The experiments will start with determination of the most effective PPS-AP complexes in singlet oxygen generation. Then Project participants will turn out the PPS-AP systems in preparative amounts.

The Project participants at SSCLM will analyze the efficiency of obtained complexes in photo-treatment of cell cultures of main agents of purulent infections. A microscopic investigations will conducted to reveal a mechanism of AP effects on PPS activity. The most active PPS-AP complexes will be used by Project participants at ICP and RIPC for immobilization on synthetic and natural polymer materials. Project participants at SSCLM will conduct the investigations of efficiency of such composite systems for PDT of wounds of different localizations and complexity on laboratory animals.

A character of inevitable structural submicron inhomogeneity of the surface of developed combined PDT systems will be studied by atomic force microscopy (scanning microscopes Smena and Solver-P47, NT-MDT, Zelenograd). The surface heterogeneity will be quantitatively described using the original approaches based on flicker-noise spectroscopy and multifractal analysis of chaotic surfaces.

The Project outcome will be bactericidal polymer films containing PS-AP complexes and a mobile device developed by the participants at RIPT for photodynamic treatment of damaged skin areas, such as festering wounds or burns, by a light beam with set parameters.

During the Project, its participant plan information exchange with foreign collaborators and joint discussions of obtained results.

The project accomplishment will give an opportunity to scientists and specialists from the Russian Federation, who took part in the tests of nuclear weapons and in the development of rocket materials and techniques, for re-orientation of their potential toward the peaceful activities. It will also encourage the scientists from the RF to integrate to the international scientific community, support fundamental and applied investigations for peaceful purposes and will contribute to the solution of national and international biotechnological problems. All this corresponds to the aims and directions of the ISTC activities.


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