Fatty acids penetration into human skin ex vivo: A TOF-SIMS analysis approach

Abstract

Linoleic, oleic, palmitoleic, palmitic, and stearic fatty acids (FAs) are commonly used in dermatological formulations. They differ by their structure, presence in the skin, and mode of application in pharmaceuticals and cosmetics compounding. These FAs are also known as chemical penetration enhancers, but their mechanisms of penetration enhancement and effect on barrier characteristics of the skin require additional study. In this study, the authors conducted an ex vivo analysis of the distribution of lipid components in the epidermis and dermis of human skin after applying individual FAs. The goal was to elucidate possible mechanisms of penetration enhancement and FA effects on barrier characteristics of the skin. FA penetration studies were conducted ex vivo on human skin and time-of-flight secondary ion mass spectrometry (TOF-SIMS) bioimaging analysis was performed to visualize and analyze distribution of FAs in skin sections. The current study demonstrated that TOF-SIMS imaging was effective in visualizing the distribution of linoleic, oleic, palmitoleic, palmitic, and stearic acid in the human skin ex vivo after the skin penetration experiment of individual FAs. The integration of the obtained TOF-SIMS images allowed a semiquantitative comparison of the effects induced by individual FA applications on the human skin ex vivo. FAs showed varying abilities to penetrate the skin and disorder the FAs within the skin, based on their structures and physicochemical properties. Linoleic acid penetrated the skin and changed the distribution of all the analyzed FAs. Skin treatment with palmitoleic or oleic acid increased the amounts of singular FAs in the skin. Penetration of saturated FAs was low, but it increased the detected amounts of linoleic acid in both skin layers. The results indicate that application of FAs on the skin surface induce redistribution of native FAs not only in the stratum corneum layer of epidermis but also in the lipid content of full epidermis and dermis layers. The results indicate that topically applied pharmaceutical products should be evaluated for potential chemical penetration enhancement and lipid component redistribution effects during formulation.

Skin Penetration Enhancement by Natural Oils for Dihydroquercetin Delivery

“…All skin samples were obtained from the same patient to avoid inter-individual variability. The control sample data was taken from our previously published research, since the skin samples were obtained from the same patient and skin area [ 19 ]. Control sample data was reprocessed along with the data of skin samples treated with natural oils.…”

“…This method provides high spatial resolution and repeatability which was confirmed by numerous studies [ 12 , 13 , 14 , 15 , 16 ], and can also be used for semi-quantitative measurements [ 17 , 18 ]. Our previous studies demonstrated suitability of TOF-SIMS bioimaging for spatial distribution analysis and semi-quantitative evaluation of selected individual FAs in human skin ex vivo [ 19 , 20 ]. In the current study, this method was used to analyze the skin penetration analysis of natural oils.…”

Mass Spectrometry in Cosmetic Science: Advanced Ionization Techniques for Detecting Trace Molecules in or on Human Skin

“…13) To date, applications of MSI to skin samples have mostly used time-of-ight secondary-ion mass spectroscopy (TOF-SIMS) and matrix-assisted laser desorption-ionization MSI (MALDI-MSI), presumably because of the broader interests in applications that provide high spatial resolution. [19][20][21] In fact, TOF-SIMS has been used for MSI analysis with submicron resolution, whereas, due primarily to the intrinsic characteristics of the ionization method used, the targets are limited to low-molecular-weight compounds. 19) Conversely, MALDI-MSI o ers relatively modest spatial resolution (~micron level) but permits the analysis of midto high-molecular-weight macromolecules (i.e., proteins and polymers) and gives more options for advanced analysis by MS such as MS/MS and/or high-resolution m/z measurements.…”

“…[19][20][21] In fact, TOF-SIMS has been used for MSI analysis with submicron resolution, whereas, due primarily to the intrinsic characteristics of the ionization method used, the targets are limited to low-molecular-weight compounds. 19) Conversely, MALDI-MSI o ers relatively modest spatial resolution (~micron level) but permits the analysis of midto high-molecular-weight macromolecules (i.e., proteins and polymers) and gives more options for advanced analysis by MS such as MS/MS and/or high-resolution m/z measurements. To the best of our knowledge, only few studies have applied 2D-DESI MSI to the analysis of substances in skin samples, 22) excluding the direct or indirect (o ine) pro ling (non-imaging) of the surface of skin in forensic, 23) security, 24) and healthcare studies.…”

Improved Transport of Adenosine Incorporated in Lipid Nanoparticles across Reconstructed Human Epidermis

“…Free fatty acid, one of the intercellular lipids in the stratum corneum, could demonstrably promote the skin penetration of poorly penetrable drugs. 9 In addition, free fatty acids are reported to maintain skin moisture when absorbed into the stratum corneum. 4 Hence, in this study, we employed free fatty acid to fabricate LNs to deliver AD to the skin.…”