Abstract

Non-invasive methods for early diagnosis of skin cancer are highly valued. One possible approach is to monitor relevant biomarkers such as tryptophan (Trp) and kynurenine (Kyn), on the skin surface. The primary aim of this in vitro investigation was, therefore, to examine whether reverse iontophoresis (RI) can enhance the extraction of Trp and Kyn, and to demonstrate how the Trp/Kyn ratio acquired from the skin surface reflects that in the epidermal tissue. The study also explored whether the pH of the receiver medium impacted on extraction efficiency, and assessed the suitability of a bicontinuous cubic liquid crystal as an alternative to a simple buffer solution for this purpose. RI substantially enhanced the extraction of Trp and Kyn, in particular towards the cathode. The Trp/Kyn ratio obtained on the surface matched that in the viable skin. Increasing the receiver solution pH from 4 to 9 improved extraction of both analytes, but did not significantly change the Trp/Kyn ratio. RI extraction of Trp and Kyn into the cubic liquid crystal was comparable to that achieved with simple aqueous receiver solutions. We conclude that RI offers a potential for non-invasive sampling of low-molecular weight biomarkers and further investigations in vivo are therefore warranted.

Highlights

  • Non-melanoma skin cancers (NMSCs), such as basal-cell carcinoma (BCC) and squamous cell carcinoma (SCC), are the most common forms of skin cancer [1]; in contrast, the melanoma-related skin cancers are less common, but more dangerous, and have become one of the fastest-growing forms of the disease [2]

  • The level of endogenous Trp deduced from these experiments was in good agreement with previous estimates reported in the literature [41,57] from both iontophoretic and passive extraction

  • The extraction of Trp and Kyn was significantly enhanced by reverse iontophoresis, and in the anode-to-cathode direction

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Summary

Introduction

Non-melanoma skin cancers (NMSCs), such as basal-cell carcinoma (BCC) and squamous cell carcinoma (SCC), are the most common forms of skin cancer [1]; in contrast, the melanoma-related skin cancers are less common, but more dangerous (due to their ability to spread to other organs), and have become one of the fastest-growing forms of the disease [2]. The current gold standard for skin cancer diagnosis relies primarily on visual inspection of a lesion followed by tissue biopsy and staining. The accuracy of this approach depends on factors such as clinician experience and lesion characteristics [4], and is reported to vary between 49 and 81% [5,6,7,8,9]. For early-stage melanoma, the current gold standard diagnostic procedure has low specificity (

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