MALDI imaging facilitates new topical drug development process by determining quantitative skin distribution profiles

Area of Science:

• Pharmacology and Pharmaceutical Sciences
• Analytical Chemistry
• Dermatology

Background:

• Accurate drug concentration determination and skin distribution profiling are vital for topical drug development, particularly for conditions like psoriasis and atopic dermatitis.
• Mass spectrometric imaging (MSI) provides the necessary spatial resolution to visualize drug distribution within skin tissue.
• Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is a powerful tool for this purpose.

Purpose of the Study:

• To quantitatively assess skin distribution profiles of four distinct drug molecules (roflumilast, tofacitinib, ruxolitinib, LEO 29102) with varying physicochemical properties.
• To evaluate the impact of different formulations on drug penetration using tofacitinib as a model.
• To demonstrate the utility of MALDI-MSI as a screening tool in topical drug product development.

Main Methods:

• Utilized matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) on human skin explant cross-sections.
• Quantified drug distribution using tissue extinction coefficient (TEC) determinations.
• Analyzed four drug molecules and two formulations of tofacitinib.

Main Results:

• MALDI-MSI successfully generated quantitative skin distribution profiles for the studied drug molecules.
• Observed distinct penetration profiles for the four drug molecules and the two tofacitinib formulations, highlighting differences in skin permeation.
• Found an inverse correlation between MALDI-MSI sensitivity and drug molecules' tissue binding affinity (estimated by Log D values).

Conclusions:

• MALDI-MSI is a valuable and applicable screening tool for evaluating drug distribution and formulation performance in topical product development.
• The technique can differentiate the skin penetration characteristics of various drug molecules and formulations.
• Drug-tissue binding affinity influences the sensitivity of MALDI-MSI analysis for topical drug distribution studies.