Characterizing Cutaneous Drug Delivery Using Open-Flow Microperfusion and Mass Spectrometry Imaging

Area of Science:

• Pharmacology
• Dermatology
• Analytical Chemistry

Background:

• Traditional methods for studying cutaneous drug delivery, such as skin accumulation and permeation, offer limited insight into drug-skin interactions.
• Advanced techniques are needed to provide a more detailed understanding of how drugs interact with and distribute within the skin.

Purpose of the Study:

• To evaluate the utility of dermal open-flow microperfusion (dOFM) and matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) for time- and depth-resolved pharmacokinetic profiling of Janus Kinase (JAK) inhibitors.
• To compare the skin distribution and pharmacokinetic profiles of two JAK inhibitors, tofacitinib and LEO 37319A, using these advanced techniques.

Main Methods:

• Time-resolved skin profiling was conducted using dermal open-flow microperfusion (dOFM) in ex vivo and in vivo pig skin models.
• Depth-resolved skin distribution of JAK inhibitors was investigated using matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) in ex vivo human skin.

Main Results:

• dOFM revealed higher skin concentrations for tofacitinib compared to LEO 37319A, correlating with physicochemical properties like molecular weight, solubility, lipophilicity, and protein binding.
• MALDI-MSI demonstrated distinct skin distribution patterns for the two JAK inhibitors, suggesting differences in their interaction with skin compartments.

Conclusions:

• dOFM and MALDI-MSI are effective complementary techniques for assessing time- and depth-resolved skin concentrations of drugs.
• These methods provide valuable data to differentiate pharmacokinetic profiles of JAK inhibitors and support decision-making in drug development.