Stimulated Raman scattering (SRS) microscopy enables label-free and quantitative imaging of active pharmaceutical ingredients within the skin, with superior chemical specificity and spatial and temporal resolution. Here, we present a method to study topical formulations on ex vivo human skin using two modalities, SRS and near-infrared light (NIR) transmission. NIR transmission is used to compensate for the SRS signal variance caused by differences in skin thickness and formulation properties. Optical co-registration of the two modalities enables recording the variance in each pixel. The developed method helps to evaluate the cutaneous pharmacokinetics of tretinoin from tretinoin-containing solution and cream formulations.
Systemic drug delivery for dermatological conditions yields little drug to the intended site of action resulting in adverse effects. Topical drug delivery is a viable alternative yet the local cutaneous pharmacokinetics (cPK) is relatively under-explored. Product dosing is dependent upon the knowledge of the dose-cPK relationship, which coincides with the pharmacodynamic (PD) activity. Coherent Raman imaging (CRI) can quantify tissue-specific drug localization and elucidate micro-scale cPK estimates, affording a clinically relevant cPK-PD relationship. This demonstration of a dose-cPK relationship utilizing CRI offers a stepping stone for additional formulation evaluation ex vivo.
We present high-speed multicolor stimulated Raman scattering imaging (SRS) enabled by an all-fiber light source. With a relative intensity noise level of -157 dBc above 10 MHz the light source is shot-noise limited up to a detector current of 0.75 mA. Compared to other fiber-based light sources optimized for SRS, the presented system is tunable in under 5 ms per arbitrary step between 700 and 3530 wavenumbers. The compact and environmentally stable system is predestined for fast multicolor assessments of medical or rapidly evolving samples with high chemical specificity.
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