Zinc is a trace element, and it is not synthesized by the human body. The element was identified in the 1960s as being essential for human health and development. Zinc is a cofactor in more than 300 enzymes necessary for cell function. In the dermatologic realm, zinc deficiency has been associated with skin alterations, delayed wound healing, and hair loss.
Zinc oxide (ZnO) is a metal oxide that also has a broad profile in dermatology. It is perhaps best known as a physical sunscreen ingredient. ZnO and titanium dioxide (TiO2) have long been used in this manner. Both ZnO and TiO2 also have been increasingly used to replace large-particle compounds in numerous cosmetics and sunscreens. These two compounds have demonstrated effective protection against UV-induced damage, providing stronger protection against UV radiation while leaving less white residue than previous generations of physical sunscreens.
Particles of ZnO in earlier sunscreens were found to be too large to penetrate the stratum corneum and, thus, were deemed biologically inactive (J. Am. Acad. Dermatol. 1999;40:85-90). However, in novel nanoparticle form, such metal oxides absorb UV radiation, leading to photocatalysis and the release of reactive oxygen species (Australas. J. Dermatol. 2011;52:1-6). Indeed, nanoparticles exhibit new physiochemical properties as a result of increased surface area as compared to large-form products, and the potential adverse effects of the novel nanoparticle formulations in sunscreens cannot be adequately extrapolated from the effects of older-generation larger-particle skin care products (J. Drugs Dermatol. 2010;9:475-81; Int. J. Dermatol. 2011;50:247-54. The relative safety of ZnO nanoparticles will be discussed in a future column. The focus in this column will be a brief comparison with TiO2 and other indications for ZnO.
ZnO and TiO2
While numerous studies explore both TiO2 and ZnO, the latter is noted for greater versatility within the dermatologic armamentarium. In addition, ZnO is less photoactive and is associated with a lower refractive index in visible light than TiO2 (1.9 vs. 2.6, respectively) (J. Am. Acad. Dermatol. 1999;40:85-90); therefore, TiO2 appears whiter and is more difficult to incorporate into transparent products.
Another important difference is the spectrum of action. That is, only avobenzone (butyl methoxydibenzoylmethane) and ZnO are approved in the United States for broad-spectrum protection against UVA wavelengths greater than 360 nm, because TiO2 has been shown to be effective only against UV wavelengths less than 360 nm (UVA is 320-400 nm). In a study by Beasley and Meyer, TiO2 delivered neither the same level of UVA attenuation nor protection from UVA to human skin as did photostabilized formulations of avobenzone or ZnO. Therefore, TiO2 is not a suitable substitute for avobenzone and ZnO for strong UVA protection (Am. J. Clin. Dermatol. 2010;11:413-21).
Indications beyond photoprotection
More than 20 years ago, Hughes and McLean showed that a ZnO tape was effective in dressing fingertip and soft tissue injuries that were resistant to healing (Arch. Emerg. Med. 1988;5:223-7). More recently, Parboteeah and Brown demonstrated the efficacy of treating recalcitrant venous leg ulcers with ZnO paste bandages (Br. J. Nurs. 2008;17:S30, S32, S34-6). In addition, Treadwell has shown that the weekly application of ZnO compression dressings to surgical wounds of the lower leg promotes healing (Dermatol. Surg. 2011;37:166-7).
Micronized zinc oxide is included in a 4% hydroquinone/10% L-ascorbic acid treatment system recently found (in a small study of 34 females) to be effective in alleviating early signs of photodamage in normal to oily skin. Thirty patients, with minimal or mild facial photodamage and hyperpigmentation, completed the 12-week treatment regimen. All the participants were satisfied with the appearance of their skin after the study, with median scores for all assessment parameters significantly improved compared with baseline (J. Drugs Dermatol. 2011;10:1455-61). ZnO also is an active ingredient in formulations intended to support the healing of perianal eczema (Hautarzt. 2010;61:33-8).
A 2001 report on a series of blinded, randomized clinical trials conducted by Baldwin et al. showed that clinical benefits were derived from the continuous topical administration of a ZnO/petrolatum formulation in a diaper introduced at that time. The first study was undertaken to verify that the ZnO/petrolatum formulation was indeed transferred from the diaper to the child’s skin. Stratum corneum (SC) samples were analyzed from each child after the wearing of a single diaper for 3 hours or multiple diapers for 24 hours. The results indicated effective transfer, with ZnO increasing in the SC from 4.2 mcg/cm2 at 3 hours to more than 8 mcg/cm2 at 24 hours.
The second study of the formulation, in an adult arm model, assessed the prevention of irritation and SC damage induced by sodium laureth sulfate. The investigators found that the ZnO/petrolatum combination yielded significant reductions in SC damage and erythema. The third study, a 4-week trial in which 268 infants were assessed, considered the effects of the formulation on erythema and diaper rash. Half of the infants wore the test diaper and half used a control diaper lacking the ZnO/petrolatum product. Significant reductions in erythema and diaper rash were indeed observed in the test group (J. Eur. Acad. Dermatol. Venereol. 2001;15 Suppl 1:5-11).