5.3. Application of Silver Nanoparticles in Dermatology

Thanks to its antimicrobial properties, silver has well-established use in dermatology. It is an active antimicrobial agent with broad-spectrum activity, so it is used to prevent and treat infections in acute wounds (such as traumatic, surgical, and burn injuries) and chronic wounds (such as diabetic foot ulcers, pressure ulcers, venous leg ulcers). When in contact with wound fluid, metallic silver salt (Ag0) becomes ionized (Ag+) and highly active against bacteria. Because only the ionized form of silver has desired antiseptic properties, contact with wound fluid is necessary if the source is metallic silver. Silver has been incorporated into various dressing products in addition to creams, gels, and barrier protectants, which differ in their solubility and the rate at which silver ions are released into the wound bed. Nanocrystalline silver dressings were launched commercially as antimicrobial dressings in 1998. They are designed for sustained silver release, releasing antibacterial silver levels for 3–7 days, resulting in less frequent re-application of silver preparations or dressings. Another benefit of silver use in modern wound management is the availability of various products for different wound situations (e.g., gauzes, hydrocolloids, hydrogels, alginates, foams). Wound characteristics which determine the choice of suitable dressing are: depth, amount of exudate, bleeding, pain. Providing a moist wound environment is an essential principle of wound healing. In addition, silver dressings appear to decrease matrix metalloproteinases that are upregulated in non-healing, chronic wounds. They may also promote cellular proliferation and re-epithelialization by inducing the production of metallothionein by epidermal cells. Metallothionein increases zinc- and copper-dependent enzymes required for cellular proliferation and matrix remodeling.

Because of numbered qualities, the use of silver dressings can reduce the treatment time and thus lead to cost savings compared to the treatment of silver-free dressings. However, published reviews found different results regarding their effectiveness. Silver-containing dressings improve the likelihood of healing venous leg ulcers, as confirmed by the 2018 Cochrane review. On the other hand, many studies found no significantly higher healing rates. Considering all that and their relatively high price, in modern wound management, the use of silver dressings is supported only if there are symptoms of wound infection.

Topical silver preparation, silver sulfadiazine (SSD) as a 1% cream, applied once to twice a day, is usually used in partial-thickness and full-thickness burns. It was discovered in the 1960s. Based on systematic reviews from 2014, 2017, and 2018, it was presumed that more advanced methods, with and without silver, lead to more improved wound healing and infection-prevention than silver sulfadiazine. Therefore, SSD is no longer so often recommended as it used to be. There is also a risk of toxicity to host cells (fibroblasts and keratinocytes). Silver sulfadiazine 1% cream is sulfa-drug, a group of synthetic antibiotics containing the sulfonamide molecular structures. Allergic reactions to sulfa drugs are among the most common drug allergies, so they should be prescribed with caution. Other uncommon adverse effects of silver sulfadiazine are hemolysis in patients with glucose-6-dehydrogenase (G6PD) deficiency, hyperosmolality, methemoglobinemia, and leukopenia (neutropenia) in children. These conditions are reversible once the cream is discontinued. Silver sulfadiazine has a low toxicity profile, but the application to large burn sites or prolonged use in bullous disorders should be avoided. Argyria is a blue-purple-gray discoloration of the skin produced by silver deposition and can be localized or generalized. Argyria is not treatable or reversible. There are also a few reported cases of argyria secondary to silver dressings. Topical incorporation of silver into the skin depends on the vehicle used, concentration, particle size and shape, substance type (depending if the source of silver is salt or nanoparticle). Smaller nanometer particles are better able to penetrate the skin than larger particles.

Another silver preparation that has widespread use in dermatology is silver nitrate (AgNO3). It is used for its caustic actions, in solid form or solutions, more durable than 5%. In clinical practice, it is often used to treat small recalcitrant ulcerations or to diminish excess granulation tissue, also called hypergranulation, which can negatively influence wound healing. Silver nitrate is also used effectively to treat warts and molluscum contagiosum, which are common viral infections, especially among children. In one study, 389 sequential patients with molluscum contagiosum were prescribed 40% silver nitrate paste with an excellent cure rate. Silver nitrate is also used to stop bleeding in small superficial wounds after curettage or shaving lesions in dermatological surgery. Although it is used because of its astringent and caustic features, caution is needed because the depth of injury can be increased.

Silver also has anti-inflammatory effects and may have angiogenic properties. Its action on the cytokine system mediates the anti-inflammatory properties of silver. Acne is a chronic inflammatory condition of the pilosebaceous units, and the Gram-positive Propionibacterium acnes bacterium is believed to have a crucial function in the pathophysiology. Because of the combination of anti-inflammatory and antimicrobial activity, it was assumed that topical silver preparations would benefit acne vulgaris. A small number of studies were conducted to test this hypothesis. Soaps with nanosilver are broadly applied in the medication of acne. In conclusion, silver preparations are often used “off-label” in this indication due to the low possibility of developing bacterial resistance, the absence of irritation, and the preservation of the skin barrier.

Atopic dermatitis (AD) is the most widespread chronic inflammatory skin disease marked by pruritus and relapsing course. It is also known as eczema and atopic eczema. More than 90% of patients with atopic dermatitis have skin colonized with Staphylococcus aureus, compared to about 5% of the unaffected individuals. Silver has an excellent antibacterial effect on S. aureus, so it is presumed to enhance AD’s clinical signs and symptoms. In a few studies, the use of silver-coated textiles in patients with AD was analyzed. Most of them demonstrated that approximately seven days of wearing such textiles could significantly diminish S. aureus density and improve AD symptoms compared with wearing cotton. On the other side, it has its disadvantages. Washing of silver-infused textiles is one of them. The amount of silver lost from textiles can range from 100% loss after four washes to less than 1%. Additionally, there is a possibility that textile silver ends up in the water supply, reducing the number of beneficial bacteria used to treat it.

Because of the increasing resistance of fungal strains, including dermatophyte strains, there is an urgent need for novel antifungals. So, the antifungal activity of AgNPs has been tested. In one study, it was effective against Trichophyton violaceum, but not against Microsporum canis or Microsporum gypseum. Mousavi et al. also found that M. canis was more resistant to silver nanoparticles. Atef et al. reported the growing inhibition of the silver nanoparticles on Trichophyton mentagrophytes and Candida albicans. Some researchers also compared the antifungal activity of AgNPs with the current antifungals. Mousavi et al. found that griseofulvin had higher anti-dermatophyte activity than silver nanoparticles. Others showed that silver nanoparticles had superior efficiency compared with fluconazole and less antifungal efficiency than griseofulvin. However, they also showed that the antifungal outcomes of fluconazole and griseofulvin were enhanced in the presence of the silver nanoparticles. In conclusion, the antifungal activity of AgNPs is yet to be confirmed with more similar studies.