In vivo quantitative molecular absorption of glycerol in human skin using coherent anti-Stokes Raman scattering (CARS) and two-photon auto-fluorescence

Sarri, Barbara; Chen, Xueqin; Simó, Rafael; Grégoire, Sébastien; Formanek, F.; Galey, Jean‐Baptiste; Potter, Anne; Bornschlögl, Thomas; Rigneault, Hervé

doi:10.1016/j.jconrel.2019.07.018

Cited by 29 publications

(21 citation statements)

References 43 publications

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“…A high spatial resolution and optimized sensitivity of detection enables CRS to precisely monitor these variations as a function of depth, which creates the basis for the accurate quantitative in vivo measurement of skin uptake. An alternative technique has recently been demonstrated using coherent anti-Stokes Raman scattering (CARS) for the in vivo quantitative penetration of deuterated glycerol in the skin [ 41 ]. The method required deuterated active ingredients to create a signal that can be detected by CARS.…”

Section: Resultsmentioning

confidence: 99%

Franz Cell Diffusion Testing and Quantitative Confocal Raman Spectroscopy: In Vitro-In Vivo Correlation

2020

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Previously, we reported the use of Confocal Raman Spectroscopy (CRS) to investigate the topical delivery of actives and excipients. We have also correlated the results from CRS with findings from in vitro diffusion studies in human skin. However, until now CRS has only been used as a semi-quantitative method of determining the skin uptake of molecules, with results expressed as arbitrary units of signal intensity. Clearly, this posed challenges for using CRS to determine skin delivery and to assess the drug bioavailability and bioequivalence of topical formulations. In the present work, the permeation of niacinamide (NIA) from various formulations in human skin was studied in vitro using conventional Franz cells and in vivo using a quantitative CRS method under finite dose conditions. The selection of NIA was based on its wide use in pharmaceutical and personal care formulations for many years. This is the first fully quantitative study to compare these methods. The vehicles investigated were neat Transcutol® P (TC); binary combinations of propylene glycol (PG) with propylene glycol monolaurate (PGML); and ternary mixtures of PG, PGML, and isopropyl myristate (IPM). These solvents were selected to encompass a range of physicochemical properties. NIA permeation was evident from all formulations in vitro and in vivo. The vehicles PG:PGML and PG:PGML:IPM delivered comparable amounts across the skin in vitro at 24 h (100.3–106.7 µg/cm2, p > 0.05) that were significantly higher compared with those of TC (1.3 µg/cm2, p < 0.05). An excellent in vitro in vivo correlation (R2 = 0.98) was found following the linear regression of the cumulative amounts of NIA permeated in vitro and the amounts of NIA at 2 μm in the skin measured with CRS. A very good correlation between the cumulative permeation of NIA in vitro and the total amount of NIA that penetrated the stratum corneum (SC) per unit of surface area (μg/cm2) in vivo was also observed, with a Pearson correlation coefficient (R2) of 0.94. The findings support the use of CRS for the quantitative measurement of actives delivered to the skin in vivo. Future studies will focus on exploring the reproducibility and reliability of the method by investigating the delivery of different actives from a wider range of vehicles. Additionally, quantitative CRS will be evaluated further as a method for assessing the bioequivalence of topical formulations.

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Section: Resultsmentioning

confidence: 99%

Franz Cell Diffusion Testing and Quantitative Confocal Raman Spectroscopy: In Vitro-In Vivo Correlation

2020

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“…Excitation was achieved with a 633 nm solid-state diode laser and 300 mW power. 25,26 Raman spectra were collected in the spectral range of 300 to 4000 cm À1 and exposure time was 10 s. When characteristic peaks of POCC and model drugs were confirmed, Raman imaging was performed in the volume scan mode. The spectrum range center was 2750 cm À1 , and exposure time was 2 s. The scanning area was 100 £ 100 mm and step was 3 mm (from 0 to 20 mm).…”

Section: Raman Imagingmentioning

confidence: 99%

A Systematic Quantitative Evaluation of Permeation Enhancement Window: Transdermal Permeation Enhancing Dynamics Establishment and Molecular Mechanisms Characterization of Permeation Enhancer

Ruan

Zhong

Zhang

et al. 2022

Journal of Pharmaceutical Sciences

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At present, transdermal permeation enhancing dynamics studies on permeation enhancers are still limited. In this study, these dynamics were established based on the content of enhancer Plurol Oleique CC in skin (C POCC ) and the increment of drug permeation amount (DQ). A new concept deemed "permeation enhancement window" (DC POCC ), comprised of a threshold dose (C thr ), maximal dose (C max ) and permeation enhancement efficiency (Eff) was used to evaluate the enhancement effect of POCC for different drugs. According to results of FT-IR, ATR-FTIR and DSC analyses, the higher CPOCC of patches containing acidic drugs vs. basic drugs resulted from their stronger interaction with pressure-sensitive adhesives, leading to more free POCC and a greater disturbing effect on stratum corneum (SC) lipids. Below C thr , a longer lag phase for acidic drugs resulted from more POCC required to compete with ceramide. When CPOCC exceeded C max by about 400 mg/g, plateau phases for all drugs were reached due to the upper limit of SC lipid fluidity, as confirmed by SAXS and Raman imaging. In summary, the differences in the permeation enhancement window for the test drugs resulted from the varied interaction strengths among POCC, drugs and adhesives, as well as changeable SC lipid fluidity.

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“…TPM relies on the non-linear photoexcitation of molecules, whereby two lowenergy photons are almost simultaneously absorbed in the same focal point, resulting in fluorescence emission [11]. Epidermal cells and extracellular matrices include a variety of endogenous fluorescent molecules, such as nicotinamide adenine dinucleotide (phosphate) (NAD(P)H), collagen, elastin, and melanin, which can be imaged by TPM non-invasively [12][13][14]. In addition, TMP imaging of exogenous fluorescent substances rhodamine-dextran provide important assessments for angiogenesis.…”

Section: Introductionmentioning

confidence: 99%

Assessing Skin Healing and Angiogenesis of Deep Burns in Vivo Using Two-Photon Microscopy in Mice

Cao

Tang

et al. 2022

Front. Phys.

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Prevalent methods for monitoring burn injuries and testing drug efficacies rely on fixed tissue sections. However, this may leave out cellular details in the living state. In vivo assessments of burn healing has been long sought after and are of scientific and clinical interest. Nicotinamide adenine dinucleotide (phosphate) (NAD(P)H), collagen, and melanin are endogenous fluorescent molecules and their signals can be captured by two-photon microscopy (TPM), therefore providing information on epidermal histological features and collagen growth in real-time. In addition, TMP imaging on exogenous fluorescent substances provides a basis for detecting blood vessels. In this work, two-photon microscopy was used to capture the exogenous fluorescent substances and endogenous fluorescent molecules at different times to assess and track burn healing in vivo. Combining TPM imaging and morphological characteristics, proliferation and differentiation of the keratinocytes in different layers of skin, collagen contents, and angiogenesis were identified and quantified. The TPM monitoring method provides an effective tool to systemically evaluate skin healing of deep burns in vivo.

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In vivo quantitative molecular absorption of glycerol in human skin using coherent anti-Stokes Raman scattering (CARS) and two-photon auto-fluorescence

Cited by 29 publications

References 43 publications

Franz Cell Diffusion Testing and Quantitative Confocal Raman Spectroscopy: In Vitro-In Vivo Correlation

Franz Cell Diffusion Testing and Quantitative Confocal Raman Spectroscopy: In Vitro-In Vivo Correlation

A Systematic Quantitative Evaluation of Permeation Enhancement Window: Transdermal Permeation Enhancing Dynamics Establishment and Molecular Mechanisms Characterization of Permeation Enhancer

Assessing Skin Healing and Angiogenesis of Deep Burns in Vivo Using Two-Photon Microscopy in Mice

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