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Use of nano silver particles in medicines
Prof O S Reddi and Dr V Ramachandra Rao | Thursday, December 15, 2016, 08:00 Hrs  [IST]

Nano-crystalline silver particles have found tremendous application in the field of high sensitivity bi-molecular detection and diagnostics, antimicrobial and therapeutics, catalysis and micro electronics.

The present production technology involves in general capital and energy – intensive processes and involves the use of environmentally hazardous chemicals like hydrazine and high-bonding solvents. Nano-crystalline silver colloids produced by aqua-chemical route exhibit aggregation with time resulting in compromisation with size factor.

Therefore what is needed is a green synthesis by environmental-friendly alternative and preferred over those aforesaid chemical methods. Thus the present method proposed utilizes environmentally friendly aqueous solvent at biological pH. Further more due to slow over kinetics which offer better manipulation and control over crystalline growth and their stabilization. Thus among these green nano-synthetic routes bio-mineralization is an alternative technique. In fact nature uses bio-mineralization to make bone, teeth, and shells. One of the biomimetic approaches is to use micro-organisms like bacteria or unicellular organisms. It leads to the deposition of silver necessitating ultra-sonication and or detergent treatment to extract the desired product.

Filamentous fungi in contrast are capable of extra synthesis facilitating downstream process and bio-mass handling easier and hence preferred over bacterial and unicellular organisms.

Filamentous fungi like Fusarium oxysporum and Aspergillus fumigates have been used for the purpose of extra cellular bio-mass free synthesis of silver nanos and are pathogenic to plants and humans which makes handling and disposal of biomass very problematic. Hence novel approach to utilize non-pathogenic fungus Trichoderma asperellum, a proven bio-control agent in agriculture is utilized.

This process yields most reproducible resulting nanos using self free aqueous filtrate from the above organism which is a non-pathogenic bio-control agent by retaining biomass intact.

Silver nano-materials use
Nano crystalline silver materials have a tremendous application in the field of sensitive bio molecular detection and diagnostics, antimicrobials and therapeutics, catalysis, electronics and medical dressings, disinfectants etc.

The development of resistance in multi-resistant pathogens has become a major problem in human medicine. For instance Staphylococcus aureus resistance to Methicillin and Candida albicans resistance to Flucanozole have received attention. On the other hand the introduction of newly devised wound dressing has been a major break through in the management of wounds and infections. In order to prevent or reduce infection a new generation of dressing material incorporating antimicrobial agents was developed. It is well established that silver ions and silver based compounds are highly toxic to microbes. Thus silver ions have been used in many kinds of formulations. It was shown that hybrids of silver nano particles with amphiphilic hyper branched macromolecules exhibit effective antimicrobial surface coating. The wound dressing impregnated with colloidal silver (Contrite H) resulted in strong decrease of pathogen – specific alterations in the infected epithelium.

The delivery of silver nanos to infected Keratinocytes in moist healing environment improves the benefit risk ratio, a compared wound dressing without silver. Similar results were obtained with E. coli.

Silver nano-materials in US medical sector
Over a decade ago (1998) NUCRYST pharmaceuticals introduced the first commercially available product namely anti microbial barrier dressing that become rapidly a clinical and commercial success that gained acceptance in burn centre across North America and it is now sold in 30 countries.

1.Antimicrobial barrier dressing
• Bacterial reduction : Inhibition of wide spectrum of bacteria including drug – resistant bacteria such as Methicillin resistant Staphylococcus aureus (MRSA) and Vancomycin Resistant Enterococcus (VRE).
• Fluid Management: Chronic wound s have differential exudates levels varying from low to high degrees. Anti microbial dressings have different degrees of absorbency in the management of exudates while helping to maintain an optimally moist wound – healing environment.
• Sustained release of silver nano crystals for a duration of seven days.
• Non – adherent space pain free removal without the disruption of the wound bed.

2. Pharmaceuticals Products
Nano crystal silver in powder form that can be combined with pharmaceuticals carries such as creams, gels, solutions, tablets to form prescription drugs.

3. Therapeutic areas
Gastrointestinal diseases
Gastrointestinal diseases market is composed of many diseases causing Heart burn, acid indigestion and bowl disorders. Many of the gastrointestinal diseases exhibit both infection and inflammation and represent targets of silver nano crystals in inflammatory bowl disorders such as ulcerative colitis and Crohn’s disease.

Ulcerative colitis
 It is characterized by inflammation and ulcers in lining of the rectum and colon which affects around five billion people in USA. Approximately US$ 500 million  were spent for medication to treat the conditions as per the report of IMS health. About half of the people diagnosed had mild symptoms. The first line of treatment for mild to moderate disease is typically from class of drugs known as five – ASAs (Amino-salicylates) which do not work in every one or may not be well tolerated.

Clostridium difficale associated disease (CDAD)
CDAD  is another important and growing medical problem the incidence of which ha doubled since 2000 USA. CDAD has become amore prominent with the increased use of Fluroquinolilne antibiotics and protein pumps inhibitors. Current treatments with Metronidazole and Vancomycin kill only the vegetable form and not the spores which are implicated in recurrence. Silver nanos act against both the vegetative and spore forms of C. difficale could and lead to a first-in-class drug that both for treatment and prevention of disease recurrence.

Scientific rationale
Noble metals are a group of metals that are resistant to corrosion and oxidation unlike base metals. Most often they include Cu – Copper, Ag – Silver, Au – Gold, Pt – platinum and occasionally Pd – Palladium.

Nobel metals also have medicinal properties and many have a current role in medicine and or medicinal devices. Silver anti microbial properties have been known for centuries. Gold has anti-inflammatory properties and was the first disease modifier for treatment in Rheumatoid arthritis. Gold is used in dental restoration. Platinum, Palladium and Radium are part of platinum group materials used in cancer chemotherapy radiation therapy.

Silver nanos useful in killing microbes
Silver nano is anti-microbial due to the release of silver ions on the surface of silver molecules that are harmless to people. Application of silver nanos is the best way to kill microbes. From ancient times to the American settlers, silver was used as preservative for drinking water and the storage of liquids. Decades ago doctors would apply a thin layer of silver to large wounds to prevent infection and promote healing. Silver became less used with the advent of penicillin and other classes of antibiotics that followed penicillin.

The growing incidence of multidrug resistant bacteria has become an acute problem through the indiscriminate use of antibiotics that has finally led to the renewed interest of the antimicrobial properties of silver. Silver nanos have received great attention due to their attractive physic-chemical properties. The surface plasma resonance and large effective scattering of individual silver nanos make them the ideal candidates for molecular labeling also.

Production of silver nanos
 The most economic route for the production of silver nanos is the microbial production over the presently available capital and energy intensive processes. Microbial route using Trichoderma asperellum is the green synthesis route which is an environmental-friendly, clean and economical.

Mode of action
Silver ions rapidly kill the microbes in a variety of ways like blocking the cell respiration pathway, interference with the components of microbial electron transport system that has effect with bacterial signal transduction, binding to DNA and inhibition of DNA replication. Silver ions bind at molecular level the effect of which does not wear off, can not be neutralized by sweat or detergents and continues to work as long as the product exists.

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