RAMOT at Tel Aviv University Ltd.

Silver-enzyme hybrids for the treatment bacterial and fungal biofilms in chronic wounds, burns and surgical wounds

Posted by RAMOT at Tel Aviv University Ltd.Responsive · Innovative Products and Technologies · Israel

Summary of the technology

Silver exhibit antibacterial activity in either ionic or metallic forms, albeit by two different mechanisms: silver ions penetrating the bacterial cell interact with the respiratory chain and with cellular DNA. Metallic silver – mostly applied as silver nano-crystals – affects primarily cell membrane by physically 'puncturing' it or by slow release of silver ions resulting from oxidative environment. Both forms - silver nano-crystals or silver ions attached to ion exchanging polymers, mostly applied as impregnated dressings, suffer from poor migration from the supplied 'reservoir' to and into their targeted microbial biofilm. While ionic silver has poor migration due to interaction with chloride and other anions, resulting in insoluble salt precipitation, silver nano crystals migration is physically restricted.
We have recently developed novel protein-silver hybrids, comprised of a biologically active glucose oxidase core, coated with a thin (~1.5nm) outer layer of metallic silver. The silver-glucose oxidase hybrid retains enzymatic activity and serves as a unique antibacterial agent, generating silver ions in situ. The soluble silver–glucose oxidase hybrid diffuses into the targeted biofilm vicinity and penetrate into its larger pores. Upon scavenging of glucose traces inside the biofilm, the glucose oxidase core of the hybrid produces hydrogen peroxide, capable of locally oxidizing and dissolving metallic silver, thus affecting enzymatically attenuated in situ silver ions release from the hybrid's silver coating into the immediate vicinity of the targeted cells, resulting in effective disinfection.
Project ID : 10-2011-255

Technology
The silver-enzyme hybrid cream is a formulation consisting of soluble, single glucose oxidase molecules coated with thin (~1.5nm) metallic silver coating. This formulation will penetrate into mixed microbial biofilms and affect their eradication by an enzymatically attenuated "triple action" mechanism: (1) glucose depletion; (2) hydrogen peroxide production; and (3) on-site silver ions release. The efficacy of this solution was demonstrated in vitro on E. coli biofilms. This cream can be used for the prevention and treatment of infected wounds.

The Need
Persistent infections present a major hurdle in the treatment of chronic wounds, surgical wounds and burns. As most of these infections are comprised of mixed cultures, wide-spectrum antimicrobial agents are required for their eradication. These include oxidizing agents, cationic polymers and silver. Silver, either in ionic or metallic form, is considered to be the safest, with rarely observed adverse effects.

Silver exhibits antibacterial activity (ionic or metallic) by two different mechanisms. Silver ions penetrating the bacterial cell interact with the respiratory chain and with cellular DNA. Metallic silver affects primarily cell membrane by physically 'puncturing' it or by slow release of silver ions resulting from oxidative environment. Metallic silver-impregnated wound dressings suffer from poor silver ion migration from the supplied 'reservoir' to and into their targeted microbial biofilm. Ionic silver has poor migration due to interaction with chloride and other anions, resulting in insoluble salt precipitation.

Stage of Development
Controlled Metallization of Glucose Oxidase: molecular silver-glucose oxidase hybrids retained their solubility and biological activities (SOPs)

in vitro efficacy: The feasibility of using these hybrids for therapeutic and preventive applications was demonstrated on E. coli (MIC, ZOI, glucose dose response)

Patent Status:
WO 2006/080017: Granted (France, Germany UK); US (pending)


Project manager

Rona Samler
VP, BD Physical Science, Medical Device, Chemistry

Project researchers

Amihay Freeman
T.A.U Tel Aviv University, Life Sciences
Molecular Microbiology-Biotechnology

Noa Hadar
T.A.U Tel Aviv University, Life Sciences
Molecular Microbiology-Biotechnology

Related keywords

  • Micro- and Nanotechnology
  • Medicine, Human Health
  • Medical Technology / Biomedical Engineering
  • Biology / Biotechnology
  • Cellular and Molecular Biology Technology
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  • Microbiology Market
  • Micro- and Nanotechnology related to Biological sciences
  • Biochemistry / Biophysics Market
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  • Cellular and Molecular Biology Market
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  • Therapeutic
  • Clinical Medicine
  • Pharmaceutical Indications
  • Pharmaceutical Indications
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About RAMOT at Tel Aviv University Ltd.

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