IONSIL GEL

Indications

• Management of wounds
• Burn treatment
• Dental caries prevention
• Topical antiseptic
• Infection control in medical devices

Dosage

Children: Refer to BNF for Children for age-appropriate dosing recommendations.

Adults: Refer to BNF for specific dosing guidelines depending on the clinical context and formulation used.

Mechanism of action

Silver ions precipitate with chloride or phosphate anions and bind to proteins, leading to antibacterial effects by disrupting cell membranes. They can bind to peptidoglycans in bacterial cell walls, causing loss of structural integrity and function. Silver also binds to and oxidizes sulphydryl groups in enzymes, inhibiting metabolic processes. Additionally, silver ions may attach to bacterial DNA, inhibiting replication, and silver nanoparticles can generate reactive oxygen species, causing oxidative stress.

Pharmacodynamics

Silver exhibits broad-spectrum antimicrobial activity, effective against both Gram-positive and Gram-negative bacteria, including _Streptococcus mutans_, _Staphylococcus aureus_, and _Escherichia coli_. It has shown dose-dependent effects against methicillin-resistant Staphylococcus aureus (MRSA). Furthermore, silver compounds have demonstrated anti-inflammatory properties in models of skin inflammation and ulcerative colitis, suppressing pro-inflammatory cytokines and matrix metalloproteinases.

Pharmacokinetics

Silver does not have a well-defined pharmacokinetic profile due to its nature as a metal; however, it is known to bind extensively to proteins and tissues. Chronic exposure to silver can lead to accumulation and potential toxicity. The absorption and distribution of silver ions can vary based on the form of silver administered, with nanoparticles showing different properties compared to ionic silver.

Pregnancy

Safety during pregnancy has not been established. Use only if clearly needed.

Breast-feeding

Caution is advised as it is not known whether silver is excreted in human milk.

Storage

Store in a well-closed container, protected from light, at room temperature.

Formulations

• Silver nitrate
• Nanocrystalline silver

Mechanism of action

The majority of released silver ions precipitate with chloride or phosphate anions or bind to albumins, macroglobulins, or tissue debris. While bound silver ions do not exert antibacterial actions, they may potentially play a role in silver toxicity in case of chronic exposure. Silver ions mediate antibacterial effects via disrupting the bacterial, fungal, and protozoal cell membranes; they bind to disulphide in membrane proteins, readily allowing penetration through the membranes and intracellular absorption via pinocytosis. They may also bind to negatively-charged peptidoglycans in the cell wall via electrostatic interactions, leading to disruption of membrane transport function and loss of structural integrity. Silver ions also bind to and oxidize sulphydryl groups (SH) in bacterial cytoplasmic enzymes to aberrate their function in metabolic processes. Silver nanoparticles may cause an increase in reactive oxygen species (ROS) inside the microbial cells leading to metal-induced oxidative stress and cell damage. They also modulate cellular signal system via inhibition of phosphorylation of essential bacterial proteins to eventually cause cell death. It is also reported that silver ions also attach to guanine in bacterial DNA, which inhibits DNA replication. While it is not fully understood, the mode of action of silver compounds in preventing and arresting dental caries is thought to involve inhibition of the demineralization process in addition to cytoplasmic and membrane function perturbation mentioned above. Silver compounds may directly interact with hydroxyapatite, a major tooth component. Light catalyzes the reduction of silver salts deposited in skin to metallic silver & it /is/ subsequently oxidized to silver sulfide; it is the deposition of the latter compound which accounts for the gray discoloration pathognomonic of argyria. /Silver and compounds/ Silver nanoparticles (nano-Ag) are potent and broad-spectrum antimicrobial agents. In this study, spherical nano-Ag (average diameter = 9.3 nm) particles were synthesized using a borohydride reduction method and the mode of their antibacterial action against E. coli was investigated by proteomic approaches (2-DE and MS identification), conducted in parallel to analyses involving solutions of Ag(+) ions. The proteomic data revealed that a short exposure of E. coli cells to antibacterial concentrations of nano-Ag resulted in an accumulation of envelope protein precursors, indicative of the dissipation of proton motive force. Consistent with these proteomic findings, nano-Ag were shown to destabilize the outer membrane, collapse the plasma membrane potential and deplete the levels of intracellular ATP. The mode of action of nano-Ag was also found to be similar to that of Ag(+) ions ... however, the effective concentrations of nano-Ag and Ag(+) ions were at nanomolar and micromolar levels, respectively. Nano-Ag appear to be an efficient physicochemical system conferring antimicrobial silver activities.

Pharmacodynamics

Silver exhibits a broad-spectrum antimicrobial activity. Silver ions were shown to mediate an effective antibacterial action against _Streptococcus mutans_, one of major bacteria present in the human oral cavity and one of etiological microorganism of dental caries. A study reported a dose-dependent antimicrobial activity of silver nanoparticles against MRSA and non-MRSA bacteria. Silver nanoparticles were also shown to mediate antibacterial activity against Gram-positive _S. aureus_ and Gram-negative _E. coli_ by inhibiting the growth. In experimental dinitrochlorobenzene-induced inflammatory models in porcine or murine skin, topical application of silver nitrate and nanocrystalline silver were shown to exert anti-inflammatory effects associated with lymphocyte apoptosis, decreased expression of pro-inflammatory cytokines, and reduced gelatinase activity. In a rat model of ulcerative colitis, orally or intracolonically administered nanocrystalline silver were shown to suppress matrix metalloproteinase (MMP-9), tumour necrosis factor (TNF), and interleukin-β (IL-β) and IL-12.

Mechanism of action

To elucidate the possible mechanism of initiation of lipid peroxidation in silver nitrate treated erythrocytes, the effect of AgNO3 on Hb catalyzed peroxidation of phospholipid liposomes was studied. Ag+ significantly increases the rate of Hb-catalyzed peroxidation. The inhibition of this effect by superoxide dismutase and catalase suggests that superoxide radical and H2O2 are involved. It was demonstrated also that Ag+ potentiates the Hb autoxidation and increases the binding of Hb to the erythrocyte membrane. Silver nitrate exhibits antiseptic, germicidal, astringent, and caustic or escharotic activity. These effects may result from silver ions readily combining with sulfhydryl, carboxyl, phosphate, amino, and other biologically important chemical groups. When silver ions interact with proteins, physical properties of the protein are usually altered; the protein may be denatured and precipitation usually occurs. Silver ions act on the surface of bacteria causing substantial changes in the cell wall and membrane. The germicidal activity of silver nitrate may be attributed to precipitation of bacterial proteins by liberated silver ions.