Topical L-Ascorbic Acid Formulation for a Better Management of Non-Melanoma Skin Cancer: Perspective for Treatment Strategies

Abstract

L-ascorbic acid, is a well-known molecule, sometimes used as antioxidant for skin care. Nonetheless, few studies have taken in account its utility as topical treatment for non-melanoma skin vancer. Non-melanoma skin cancer includes basal cell carcinoma and squamous cell carcinoma and is widespread worldwide with an increasing incidence. The purpose of this paper is to analyze the characteristics of L-ascorbic acid topical formulation, its percutaneous absorption and biochemical mechanism, focusing on its anti-cancer properties. In particular, it will be described how the pH and the concentration of the formulation are able to influence its distribution in the skin and tissues. We will report, the current knowledge on the pharmacokinetic aspects of L-ascorbic acid that allows us to reconsider it in the light of its ability to act as a prodrug and as an anticancer agent. Lastly, a short review with the aim to find any evidence of a possible clinical use of L-ascorbic acid for the treatment of non-melanoma skin cancer was made.

Keywords: L-ascorbic acid (AA); ascorbyl radical (Asc •); basal cell carcinoma (BCC); biodistribution; hydrogen peroxide (H2O2); non-melanoma skin cancer (NMSC); pharmacokinetics; skin cancer; squamous cell carcinoma (SCC); topical formulation.

Figure 1

Conversion of the mono anion form of AA in Asc • by the transfer of an electron. The stability of the Asc • is due by the unpaired electron delocalized in the tricarboxylic ring.

Figure 2

Ox-redox states of ascorbic acid.

Figure 3

Enlarged representation of the skin. In pink, the layer of the dermis, supplied by blood vessels that allow the transport of nutrients towards the epidermis in dark purple.

Figure 4

Only the protonated form AscH₂ is able to cross biological membranes by passive diffusion. The monoanionic form is unable to pass lipid membranes.