Ascorbic acid 2‐glucoside: An ascorbic acid pro‐drug with longer‐term antioxidant efficacy in skin

Abstract

Objective Deleterious effects of pollutants and ultraviolet radiation on the skin can be attenuated using formulations containing antioxidants. However, these have disadvantages, including chemical instability, photodegradation, poor bioavailability or biological activity. Here, two commercial formulations were evaluated: one optimized to stabilize and deliver ascorbic acid (AA) at 15% and the other containing a glucoside form of AA, namely ascorbic acid 2‐glucoside (AA2G), at 1.8% and at a physiological pH. We compared the skin delivery, antioxidative effects and chemical stability of AA2G with AA in their respective formulations. Methods Skin delivery was measured using fresh viable human skin explants, and oxidative stress was measured using a human reconstructed epidermal (RHE) model according to levels of malondialdehyde (MDA), superoxide dismutase (SOD) and catalase. Results Ascorbic acid 2‐glucoside was completely metabolized to AA by the skin before entering the receptor compartment. The skin contained parent and AA, indicating a reserve of AA2G was present for further metabolism. For AA2G and AA, maximum flux of AA‐equivalents was at 12 h, with continued absorption over 24 h. The absolute amount in µg was higher in the skin after application of AA than after application of AA2G. This may suggest a greater antioxidative effect; however, according to all three measurements of oxidative stress, the protective effect of AA and AA2G was similar. Unlike AA, AA2G was chemically stable under storage conditions. Conclusion A lower concentration of AA2G is as effective as the active metabolite, AA, in terms of antioxidant effects. AA2G was chemically stable and can be applied at a lower concentration than AA, thus avoiding the need for an acidic formulation with a pH below 3.5.

Efficient dermal delivery of ascorbic acid 2‐glucoside with photoacoustic waves

“…The significant decrease in vitamin C stability was observed after incubation at 37°C for 20 min followed by a pH adjust to 9.0 immediately before HPLC injection. This is consistent with other reports showing that vitamin C is only stable in acidic formulations with pH below 3.5 [8].…”

“…The s factor is related to the possible conversion of AA2G to vitamin C, and subsequent degradation of vitamin C, as AA2G diffuses through the skin sample. A recent study using viable human skin explants showed that AA2G is completely metabolized to vitamin C during passive diffusion through 450 μm thick skin [8]. This is consistent with our results of passive diffusion shown in Figure 6a, although under our experimental conditions vitamin C is not stable and was not quantified.…”

“…Besides the anti-hyperpigmentation properties, AA is also a well-established skin anti-ageing component due to its stimulatory effect in collagen synthesis and antioxidant protection against UV-induced oxidative stress [2,3]. However, its anti-ageing properties are strongly affected by its low stability under certain conditions such as exposition to light, air, metal ions, heat, and pH higher than 3.5, limiting its use in the development of cosmetic formulations [6][7][8]. Some AA precursors can overcome these limitations and are commonly used by the cosmetic industry [7].…”

Ascorbic Acid (Vitamin C) as a Cosmeceutical to Increase Dermal Collagen for Skin Antiaging Purposes: Emerging Combination Therapies

“…Because this compound has strong hydrophilicity, its skin permeability is lower than that of AA [ 93 ]. This compound is relatively stable in the cosmetic formulation and, when topically applied, it can be enzymatically hydrolyzed in the skin, producing AA [ 93 , 94 ].…”

“…In summary, certain hydrophobic AA precursors could be more effective than AA itself in increasing the concentration of AA in the cytoplasm because it is easy to pass through the cell membrane [ 83 , 88 ]. Topically applied AA glycosides can serve as a reservoir for AA because they continuously release AA by enzymatic hydrolysis in the skin [ 94 ]. Multifunctional hybrid compounds developed by covalently combining two substances with different biological activities and physicochemical properties would have added benefits [ 84 , 87 ].…”