Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 607, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.ijpharm.2021.120967
Keywords
Molecular imaging; DESI-MSI; Biodistribution; Skin; Topical delivery; Bioequivalence
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Funding
- University of Geneva for teaching assistantships for Julie Quartier and Maria Lapteva
- Societe Academique de Geneve
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By utilizing desorption electrospray ionization mass spectrometry imaging (DESI-MSI), the spatial distributions of drugs and excipients in the skin can be investigated, providing insights into drug penetration pathways when combined with skin structures and endogenous components.
The cutaneous biodistribution method (CBM) yields a high-resolution quantitative profile of drug deposition as a function of skin depth. However, it provides limited details about drug spatial distribution or penetration pathways. Mass spectrometry imaging (MSI) can complement the detailed quantitative data generated by CBM studies. The objectives of this work were to use desorption electrospray ionization (DESI)-MSI to (i) investigate the spatial cutaneous distributions of a topically applied drug and excipient and relate them to skin structures and (ii) image endogenous skin components and combine these results to gain insight into drug penetration routes. Porcine skin was used to compare two bioequivalent creams of econazole nitrate (ECZ) and a micelle formulation based on D-alpha-tocopheryl succinate polyethylene glycol 1000 (TPGS). DESI-MSI successfully imaged the cutaneous spatial distribution of ECZ and TPGS in 40 pm-thick horizontal sections and vertical cross-sections of the skin. Interestingly, clinically bioequivalent formulations did not appear to exhibit the same molecular distribution of ECZ in XY-horizontal sections. DESI-MSI also enabled visualization of TPGS (m/z 772.4706), mainly in the upper epidermis (<= 80 pm). In conclusion, through co-localization of drugs and excipients with endogenous elements of the skin, DESI-MSI could further our understanding of the cutaneous penetration pathways of xenobiotics.
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