Label-free skin penetration analysis using time-resolved, phase-modulated stimulated Raman scattering microscopy.

Area of Science:

• Biomedical Optics
• Chemical Imaging
• Pharmacokinetics

Background:

• Skin penetration analysis is crucial for topical drug and active compound delivery.
• Conventional Stimulated Raman Scattering (SRS) microscopy has limitations in signal contrast for low-concentration imaging due to background signals.
• Label-free imaging techniques are desired for non-invasive analysis of skin penetration.

Purpose of the Study:

• To develop and validate a novel phase-modulated SRS (PM-SRS) microscopy method for enhanced skin penetration analysis.
• To improve signal contrast and overcome limitations of conventional SRS microscopy in imaging low-concentration substances in skin.
• To demonstrate the capability of PM-SRS for quantitative pharmacokinetic monitoring of topical agents.

Main Methods:

• Utilized phase-modulated SRS (PM-SRS) microscopy with phase modulation and time-resolved signal detection.
• Implemented PM-SRS to suppress nonlinear and Raman background signals in biological tissues.
• Conducted proof-of-concept experiments using ectoine (moisturizing agent) and loxoprofen sodium (therapeutic drug) in an in vitro skin model.

Main Results:

• PM-SRS achieved a 40-fold increase in signal contrast compared to conventional amplitude-modulated SRS (AM-SRS) using a 1.7-ps probe delay.
• Successfully measured the skin penetration of loxoprofen sodium, with a mean concentration of 47.3 ± 4.8 mM at the tissue surface after 240 minutes.
• Demonstrated the ability to monitor drug concentration in the millimolar range.

Conclusions:

• PM-SRS microscopy is a powerful tool for label-free skin penetration analysis of topical agents.
• The enhanced contrast and sensitivity of PM-SRS enable imaging of low-concentration drugs and pharmacokinetic studies.
• This technique holds significant potential for advancing topical drug delivery research and development.