Novel insights into ascorbic acid skin permeation

Mistry, Jatin (2020) Novel insights into ascorbic acid skin permeation. PhD thesis, University of Nottingham.

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Ascorbic acid (vitamin C) is a popular topically applied cosmeceutical due to its antioxidative, photoprotective, antiaging and antipigmentary effects. Despite these beneficial effects to the skin, instability of ascorbic acid in aqueous solution has directed formulation scientists to focus on stable ascorbic acid derivatives that can be used in topical preparations. However, these derivatives are required to be metabolised by the skin to the active, free-acid form to observe efficacy. Accordingly, current knowledge regarding skin permeation of ascorbic acid is limited, with in vivo human skin permeation data unavailable.

The aim of this work was to use imaging techniques, specifically time of flight-secondary ion mass spectrometry (ToF-SIMS), to visualise the spatial distribution of topically applied ascorbic acid in the skin without the requirement for chemical labelling. This was performed in conjunction with established analytical techniques, such as high performance liquid chromatography (HPLC), that are traditionally used for skin permeation studies to obtain absolute quantitative information but with no spatial component. This dual approach provides the opportunity to reveal new insights into ascorbic acid skin permeation that would not be possible with one analytical technique alone.

A comprehensive study comparing ascorbic acid and caffeine permeation, believed to be the first of its kind, shows how a gel formulation can retard the permeation of ascorbic acid but enhance the permeation of caffeine through ex vivo porcine skin tissue. The gel formulations were rubbed into the skin, to mimic in use conditions. When examining the spatial distribution, ascorbic acid and caffeine were found to be non-uniformly distributed and primarily localised to the epidermis. Contrary to previous reports that the follicular route contributes approximately 50% of the total in vitro skin permeation, no localisation of caffeine was observed in the hair follicle.

Nanostructured lipid carrier (NLC) formulations have been intensively investigated as topical formulation vehicles. Herein an NLC formulation, and a comparator cream formulation, were developed and tested on human skin in vivo for permeation. Analysis of tape strip samples by HPLC analysis showed the cream formulation to deliver the most ascorbic acid into the stratum corneum. However, analysis of tape strip samples from cream-treated skin, by ToF-SIMS, showed the ascorbic acid was mainly localised in the furrows of the skin. A direct correlation between ToF-SIMS and HPLC, performed for the first time, showed that for the NLC formulation, ascorbic acid was more laterally distributed over the corneocytes at all concentrations, and not just localised to skin furrows, than the cream formulation.

An ideal topical preparation should deliver the active ingredient into the corneocytes. Uncovering the spatial distribution, and localisation, of the permeant in the skin barrier has facilitated identification of the NLC formulation to be the most suitable topical preparation for ascorbic acid; and therefore, have the potential to increase the therapeutic effects observed in the skin. Dependence on the established analytical techniques, used for skin permeation studies would have resulted in an altogether different conclusion being reached.

The standard approach of using HPLC, as advised by regulatory bodies, provides limited information about skin permeation due to a lack of imaging capability. The application of imaging techniques, such as ToF-SIMS, in this work has shown unequivocally permeation behaviour different from current literature understanding and a permeation profile different from conventional chromatography based methodology. It was therefore demonstrated that information regarding spatial distribution of the permeant in the skin barrier is essential to gaining a more holistic understanding of the mechanisms and routes of skin permeation when evaluating the effectiveness of topically applied formulations.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Scurr, David
Barrett, David
Hicks, Jake
Starr, Nichola
Keywords: Ascorbic acid, skin, stratum corneum, ToF-SIMS, topical formulations, nanostructured lipid carriers, in vivo human, ex vivo porcine, tape stripping, caffeine
Subjects: R Medicine > RM Therapeutics. Pharmacology
Faculties/Schools: UK Campuses > Faculty of Science > School of Pharmacy
Item ID: 59771
Depositing User: Mistry, Jatin
Date Deposited: 16 Jul 2020 04:40
Last Modified: 16 Jul 2022 04:30

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