Abstract:The functional ingredients for skin-related products have been highly recognized accompanied by the consumers’ curiosity and instrumental improvement. The targeted location of a functional active ingredient in the skin organelle could be very critical information for its product development, safety evaluation, and benefit claims. Due to those factors, mass spectrometry technology exhibited rapid growth in those research areas because it can accurately and sensitively determine the ingredient molecular weights … Show more
“…Tape-stripping-based lowinvasive ATR-FTIR and EPR spectroscopy methods are commonly used in in vivo skin penetration studies, but require special permission and are severely limited in patients. Low-invasive methods can be applied both in vivo and ex vivo and include tape stripping, primarily applied at the SC [16][17][18]; cyanoacrylate stripping applicable to the SC and viable epidermis [18,19]; suction blister after the application of partial negative pressure on the skin with further analysis of the accumulated interstitial and serum fluids [20]; sampling of the interstitial fluid from the viable epidermis and/or dermis with microneedles [21][22][23] or by microdialysis [24,25], followed by an analysis with validated methods (or their combinations) such as autoradiography for the detection of the radioisotopelabelled penetrants [26], high-performance liquid chromatography, mass spectrometry of various modifications, or UV/VIS spectroscopy (absorption or (epi)fluorescence in a specific spectral range) [26][27][28][29][30]. The skin penetration profile can be determined using low-invasive attenuated total reflectance Fourier-transform infrared (ATR-FTIR) [31][32][33], Fourier-transform infrared photoacoustic spectroscopy (FTIR-PAS) [31], thermal emission decay-Fourier-transform infrared (TED-FTIR) spectroscopy [34], and electron paramagnetic resonance (EPR) spectroscopy [35] for the analysis of the SC removed from skin with tape or cyanoacrylate stripping.…”
Information on the penetration depth, pathways, metabolization, storage of vehicles, active pharmaceutical ingredients (APIs), and functional cosmetic ingredients (FCIs) of topically applied formulations or contaminants (substances) in skin is of great importance for understanding their interaction with skin targets, treatment efficacy, and risk assessment—a challenging task in dermatology, cosmetology, and pharmacy. Non-invasive methods for the qualitative and quantitative visualization of substances in skin in vivo are favored and limited to optical imaging and spectroscopic methods such as fluorescence/reflectance confocal laser scanning microscopy (CLSM); two-photon tomography (2PT) combined with autofluorescence (2PT-AF), fluorescence lifetime imaging (2PT-FLIM), second-harmonic generation (SHG), coherent anti-Stokes Raman scattering (CARS), and reflectance confocal microscopy (2PT-RCM); three-photon tomography (3PT); confocal Raman micro-spectroscopy (CRM); surface-enhanced Raman scattering (SERS) micro-spectroscopy; stimulated Raman scattering (SRS) microscopy; and optical coherence tomography (OCT). This review summarizes the state of the art in the use of the CLSM, 2PT, 3PT, CRM, SERS, SRS, and OCT optical methods to study skin penetration in vivo non-invasively (302 references). The advantages, limitations, possibilities, and prospects of the reviewed optical methods are comprehensively discussed. The ex vivo studies discussed are potentially translatable into in vivo measurements. The requirements for the optical properties of substances to determine their penetration into skin by certain methods are highlighted.
“…Tape-stripping-based lowinvasive ATR-FTIR and EPR spectroscopy methods are commonly used in in vivo skin penetration studies, but require special permission and are severely limited in patients. Low-invasive methods can be applied both in vivo and ex vivo and include tape stripping, primarily applied at the SC [16][17][18]; cyanoacrylate stripping applicable to the SC and viable epidermis [18,19]; suction blister after the application of partial negative pressure on the skin with further analysis of the accumulated interstitial and serum fluids [20]; sampling of the interstitial fluid from the viable epidermis and/or dermis with microneedles [21][22][23] or by microdialysis [24,25], followed by an analysis with validated methods (or their combinations) such as autoradiography for the detection of the radioisotopelabelled penetrants [26], high-performance liquid chromatography, mass spectrometry of various modifications, or UV/VIS spectroscopy (absorption or (epi)fluorescence in a specific spectral range) [26][27][28][29][30]. The skin penetration profile can be determined using low-invasive attenuated total reflectance Fourier-transform infrared (ATR-FTIR) [31][32][33], Fourier-transform infrared photoacoustic spectroscopy (FTIR-PAS) [31], thermal emission decay-Fourier-transform infrared (TED-FTIR) spectroscopy [34], and electron paramagnetic resonance (EPR) spectroscopy [35] for the analysis of the SC removed from skin with tape or cyanoacrylate stripping.…”
Information on the penetration depth, pathways, metabolization, storage of vehicles, active pharmaceutical ingredients (APIs), and functional cosmetic ingredients (FCIs) of topically applied formulations or contaminants (substances) in skin is of great importance for understanding their interaction with skin targets, treatment efficacy, and risk assessment—a challenging task in dermatology, cosmetology, and pharmacy. Non-invasive methods for the qualitative and quantitative visualization of substances in skin in vivo are favored and limited to optical imaging and spectroscopic methods such as fluorescence/reflectance confocal laser scanning microscopy (CLSM); two-photon tomography (2PT) combined with autofluorescence (2PT-AF), fluorescence lifetime imaging (2PT-FLIM), second-harmonic generation (SHG), coherent anti-Stokes Raman scattering (CARS), and reflectance confocal microscopy (2PT-RCM); three-photon tomography (3PT); confocal Raman micro-spectroscopy (CRM); surface-enhanced Raman scattering (SERS) micro-spectroscopy; stimulated Raman scattering (SRS) microscopy; and optical coherence tomography (OCT). This review summarizes the state of the art in the use of the CLSM, 2PT, 3PT, CRM, SERS, SRS, and OCT optical methods to study skin penetration in vivo non-invasively (302 references). The advantages, limitations, possibilities, and prospects of the reviewed optical methods are comprehensively discussed. The ex vivo studies discussed are potentially translatable into in vivo measurements. The requirements for the optical properties of substances to determine their penetration into skin by certain methods are highlighted.
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