**3. Anti bacterial effect of silver nanoparticles**

Due to the outbreak of the infectious diseases caused by different pathogenic bacteria and the development of antibiotic resistance the pharmaceutical companies and the researchers are searching for new antibacterial agents free of resistance and cost. In the present scenario silver nanoparticles have emerged up as novel antimicrobial agents owing to their high surface area to volume ratio and its unique chemical and physical properties. The use of silver nanoparticles can be exploited in various fields, particularly medical and pharmaceutical due to their low toxicity to human cells, high thermal stability and low volatility (Silver, 2003). This has resulted in a broad array of studies in which silver nanoparticles have played a role as drug and as well as superior anti bacterial agent. The highest synergistic antibacterial activity was observed with silver nanoparticles combined antibiotics (Raymond Wai-Yin Sun, 2005). silver nanoparticle incorporated cotton fabrics showed antibacterial activity (Shahverdi, 2007), and silver nanoparticle containing poly vinyl nano- fibres shows efficient antibacterial property (Duran, 2007), it can be used in silver dressings, creams, gel effectively reduce the bacterial infections in chronic wound (Jun, 2007; Richard, 2002; Leaper, 2006). Siver nanoparticles are reported to show better wound healing capacity, better cosmetic appearance and scarless healing when tested using an animal model (Ip, 2006). Kumar et al., 2008 investigated an eco-friendly method for synthesis of metal nanoparticles embedded paint from using vegetable oil. The paint depicts excellent antibacterial activity and in future this paint can be used for efficient antimicrobial coating agent to coat various surfaces such as wood, glass, walls. Silver has been used in water and air ltration to eliminate microorganisms, additionally the Fe3 O4 attached Ag nanoparticles can be used for the treatment of water and easily removed using magnetic field to avoid contamination in the environment (Kumar et al., 2008).

### **4. Silver nanoparticles and antibiotic resistance**

Antibiotic resistance is a type of drug resistance where a microorganism has developed the ability to survive exposure to an antibiotic. The volume of antibiotic prescribed is the major factor in increasing rates of bacterial resistance rather than compliance with antibiotics. The four main mechanisms by which microorganisms exhibit resistance to antimicrobials are: Drug inactivation or modification ( e.g. enzymatic deactivation of Penicillin G in some penicillin-resistant bacteria through the production of β-lactamases) and .alteration of target site( e.g. alteration of Penicillin-binding proteins (PBPs) —the binding target site of penicillins—in Methicillin-resistant *Staphylococcus aureus* (MRSA) and other penicillinresistant bacteria). Alteration of metabolic pathway( e.g. some sulfonamide-resistant bacteria do not require para-aminobenzoic acid (PABA), an important precursor for the synthesis of folic acid and nucleic acids in bacteria inhibited by sulfonamides. Instead, like mammalian cells, they turn to utilizing preformed folic acid) and reduced drug accumulation: by decreasing drug permeability and/or increasing active efflux (pumping out) of the drugs across the cell surface [Figure 3].

2002). Using plants for nanoparticle synthesis can be advantageous over other biological processes because it eliminates the elaborate process of maintaining cell cultures and can

Due to the outbreak of the infectious diseases caused by different pathogenic bacteria and the development of antibiotic resistance the pharmaceutical companies and the researchers are searching for new antibacterial agents free of resistance and cost. In the present scenario silver nanoparticles have emerged up as novel antimicrobial agents owing to their high surface area to volume ratio and its unique chemical and physical properties. The use of silver nanoparticles can be exploited in various fields, particularly medical and pharmaceutical due to their low toxicity to human cells, high thermal stability and low volatility (Silver, 2003). This has resulted in a broad array of studies in which silver nanoparticles have played a role as drug and as well as superior anti bacterial agent. The highest synergistic antibacterial activity was observed with silver nanoparticles combined antibiotics (Raymond Wai-Yin Sun, 2005). silver nanoparticle incorporated cotton fabrics showed antibacterial activity (Shahverdi, 2007), and silver nanoparticle containing poly vinyl nano- fibres shows efficient antibacterial property (Duran, 2007), it can be used in silver dressings, creams, gel effectively reduce the bacterial infections in chronic wound (Jun, 2007; Richard, 2002; Leaper, 2006). Siver nanoparticles are reported to show better wound healing capacity, better cosmetic appearance and scarless healing when tested using an animal model (Ip, 2006). Kumar et al., 2008 investigated an eco-friendly method for synthesis of metal nanoparticles embedded paint from using vegetable oil. The paint depicts excellent antibacterial activity and in future this paint can be used for efficient antimicrobial coating agent to coat various surfaces such as wood, glass, walls. Silver has been used in water and air ltration to eliminate microorganisms, additionally the Fe3 O4 attached Ag nanoparticles can be used for the treatment of water and easily removed using magnetic field to avoid

Antibiotic resistance is a type of drug resistance where a microorganism has developed the ability to survive exposure to an antibiotic. The volume of antibiotic prescribed is the major factor in increasing rates of bacterial resistance rather than compliance with antibiotics. The four main mechanisms by which microorganisms exhibit resistance to antimicrobials are: Drug inactivation or modification ( e.g. enzymatic deactivation of Penicillin G in some penicillin-resistant bacteria through the production of β-lactamases) and .alteration of target site( e.g. alteration of Penicillin-binding proteins (PBPs) —the binding target site of penicillins—in Methicillin-resistant *Staphylococcus aureus* (MRSA) and other penicillinresistant bacteria). Alteration of metabolic pathway( e.g. some sulfonamide-resistant bacteria do not require para-aminobenzoic acid (PABA), an important precursor for the synthesis of folic acid and nucleic acids in bacteria inhibited by sulfonamides. Instead, like mammalian cells, they turn to utilizing preformed folic acid) and reduced drug accumulation: by decreasing drug permeability and/or increasing active efflux (pumping

also be suitably scaled up for large-scale nanoparticle synthesis (Shenton, 1999)

**3. Anti bacterial effect of silver nanoparticles** 

contamination in the environment (Kumar et al., 2008).

**4. Silver nanoparticles and antibiotic resistance** 

out) of the drugs across the cell surface [Figure 3].

Fig. 3. Various mechanisms of bacterial resistance against antibacterials (G. Thirumurugan, 2011).

Therefore, an alternative way to overcome the antibiotic and drug resistance of various micro organisms is needed desperately, especially in medical devices, pharmaceutical etc. The nano size allowed expansion of the contact surface of silver with the microorganisms, and this nano scale has applicability for medical devices and pharmaceutical by surface coating agents. Kim et al., 2007 studied antibacterial mechanism of silver nanoparticles for certain microbial species. The peptidoglycan layer is a specific membrane feature of bacterial species and not mammalian cells. Therefore, if the antibacterial effect of silver nanoparticles is associated with the peptidoglycan layer, it will be easier and more specific to use silver nanoparticles as an antibacterial agent. Sondi and Salopek-Sondi, 2007 reported that the antibacterial activity of silver nanoparticles on Gram-negative bacteria was dependent on the concentration of Ag nanoparticle, and was closely associated with the formation of 'pits' in the cell wall of bacteria. Then, Ag nanoparticles accumulated in the bacterial membrane caused the permeability, resulting in cell death and they reported degradation of the membrane structure of micro organism with silver nanoparticles. Kim et al., 2007 suggested that the antimicrobial mechanism of Ag nanoparticles is related to the formation of free radicals and subsequent free radical–induced membrane damage. The free radicals may be derived from the surface of silver nanoparticles and be responsible for the antibacterial activity. In proteomic and biochemical studies, nano molar concentrations of AgNPs have killed E.coli cells within minutes possibly due to immediate dissipation of the proton motive force (Lok, 2006). This action is similar to that found for antibacterial activities of Ag+ ions (Dibrov, 2002). For example, low concentrations of Ag+ ion result in massive proton leakage through the Vibrio cholerae membrane (Dibrov, 2002). This proton leak might be happening from either any Ag+ -modied membrane protein or any Ag+-modied phospholipids

Silver Nanoparticles: Real Antibacterial Bullets 415

The antibacterial properties and the toxicity of metals to micro-organisms is well known, thus, now a days, silver is used in different kinds of formulations like surface coating agents, wound dressing, etc., (Shahverdi, 2007). The silver dressings make use of delivery systems that release silver in different concentrations. But different factors like the distribution of silver in the dressing, its chemical and physical form, affinity of dressing to moisture also inuence the killing of micro organisms (Lansdown, 2002). In this direction, metal nanocomposite bres were prepared containing silver nanoparticles incorporated inside the fabric but from the scanning electron microscopic study it was concluded that the silver nanoparticles incorporated in the sheath part of fabrics possessed signicant antibacterial property compared to the fabrics incorporated with silver nanoparticles in the core part (Chopra, 2007). Similar results were obtained by using silver nanoparticles on polyester nonwovens. It is also reported that silver nanoparticles coated textile fabrics possess

Drug delivery system provide useful adjuncts for therapeutics including drugs, nucleic acids and proteins, with variety or roles like improving poor solubility, enhancing invivo stability, optimizing the biodistribution and pharmacokinetics of drugs. In recent years, interest has been stimulated by capability of the metal nanoparticles like AgNPs to bind a wide range of organic molecules, their low toxicity, and their strong and tunable optical absorption. This has resulted in a broad array of studies in which silver nanoparticles have played a role as drug and vaccine carriers into target cells or specic tissues. Furthermore, the unique chemical, physical, and photo-physical properties of silver nanoparticles can be exploited in innovative ways to control the transport and controlled release of pharmaceutical compounds (Skirtach, 2006). Generally, this has been achieved by modifying the surface of the silver nanoparticles so that they can bind to the specic targeting drugs or other biomolecules. But direct conjucation of metal nanoparticle with drugs also possible, it has been shown that conjugates of metal nanoparticles with antibiotics provide promising results in the treatment of intracellular infections (Skirtach, 2006). The conjugation of silver nanoparticles in antibiotic can increase the effectiveness of drug delivery to target some cases. Generally, exact dose is required to kill the pathogens but the amount of antibiotic used in therapy is much higher than the actual dose required. The excess amount of antibiotic can cause adverse effects. Therefore, this conjugation of antibiotic with silver nanopaticles would be helpful to improve antibiotic efficacy. Silver nanoparticles can be directly conjugated with antibiotics or other drug molecules via ionic or covalent bonding, or by physical absorption. For example, Drug has been conjugated to silver nanoparticles [Figure 4]. The cytotoxic effect of free drug is about seven times lower than that of drug conjugated silver nanoparticles. Saha et al., 2007, conjugated directly different type of antibiotic to nonfunctionalized spherical metal nanoparticles, conjugated form showed greater degree of antibacterial activity with stability than free antibiotics. However, the conjugated form showed some aggregation after conjugation, a situation that other workers consider very deleterious. Therefore, it is likely that modication of the surface of the metal nanoparticles to prevent

antibacterialactivity against S.aureus (Shahverdi, 2007).

**6. Silver nanoparticles in antibacterial drug delivery** 

aggregation would improve the efficacy of such drug delivery systems further.

Surface chemistry of nanomaterial plays an important role, to improve the stability of metal nanoparticles and prevent their aggregation during the conjugation process between biomolecules and nanoparticles. Compared with other drug release materials, the unique

bilayer. The phenomenon causes deenergization of the membrane and consequently cell death (Dibrov, 2002). Shahverdi et al., 2007 studied the combined effect of silver nanoparticles with different antibiotics against S.aureus and E.coli using the disk diffusion method. The antibacterial activities of penicillin G, amoxicillin, erythromycin, clindamycin, and vancomycin increased in the presence of Ag-NPs against both test strains.
