• The PHA and bionic structure

Polyhydroxy acids and bionic acids are organic carboxylic acids, which possess two or more hydroxyl groups on an aliphatic or alicyclic molecular structure. When one of the hydroxyl groups occurs in the alpha position, the PHA is a polyhydroxy AHA Fig. 33.1; when an additional sugar is attached to the PHA structure, the molecule is a bionic acid (Fig. 33.1). Because they share the common AHA structure, PHAs and bionics have the ability to provide skin effects similar to traditional AHAs, such as glycolic acid.

Fig. 33.1 PHAs: gluconolactone and lactobionic acid

• Antioxidant and free radical scavenging effects of gluconolactone

The antioxidant properties of gluconolactone are evident in food and drug substances, in which gluconolactone has been shown to inhibit oxidation and help maintain product integrity Fig. 33.3.

Fig. 33.3 Antioxidant effects of PHAs: gluconolactone and lactobionic acid inhibit oxidative darkening of anthralin and hydroquinone and prevent oxidative browning of banana peels exposed to ambient conditions. Photos demonstrate the screening process

Bernstein et al demonstrated that gluconolactone provides free radical scavenging effects comparable to other well-known compounds such as ascorbic acid and alpha-tocopherol using an in vitro model of cutaneous photoaging. In this model, compounds are measured for their ability to prevent ultraviolet (UV) induced activation of an elastin promoter in skin via free radical scavenging activity. An increase in the expression of the elastin promoter causes an abnormal deposition of poorly structured elastic material in skin—the condition known as solar elastosis. Maximum protection by free radical scavengers occurs at a rate of approximately 50%; the other 50% is caused by direct UV damage to cells and cellular DNA. Results of the study indicated that gluconolactone provided up to 50% protection against UV radiation. This effect could not be explained by UV screening, and therefore was attributed to gluconolactone’s ability to chelate oxidation-promoting metals possibly via the direct free radical scavenging effects of gluconolactone.

• Clinical effects of gluconolactone

In vivo clinical studies of gluconolactone-containing formulations have demonstrated measurable benefits including antiaging and skin-firming effects that are comparable to commonly used AHAs (e.g. glycolic acid), with reduced irritation potential. In addition, significant antiaging benefits including reduced pigmentation and improved skin texture have been observed over a range of darker Fitzpatrick skin types (IV–VI) represented by a study population of African–Americans, Asians, and Hispanics.

Gluconolactone is well suited for adjunctive use with topical medications. It enhances epidermal cell turnover, which may in part help to explain the adjunctive benefits of PHAs in the treatment of acne. A vehicle-controlled, double-blind clinical study on mild to moderate acne demonstrated antiacne effects with less irritation of a 14% gluconolactone solution in comparison to a 5% benzoyl peroxide lotion. In addition, PHAs can be used to hydrate and condition skin during treatment with drying or irritating medications including topical retinoids, benzoyl peroxide, and azelaic acid. This benefit was demonstrated in a clinical study designed to evaluate the effects of standardized adjunctive use of a PHA cleanser plus PHA moisturizer in combination with 15% azelaic acid gel for the treatment of rosacea. Results indicated significantly greater improvements in global assessment and erythema relative to the azelaic acid treatment group that had not been standardized to adjunctive PHAs (P < 0.05). Compatibility of a 15% gluconolactone-containing cream (pH 3.3) in combination with daily use of tretinoin gel 0.1% has also been demonstrated.