In situ biodistribution and residency of a topical anti‐inflammatory using fluorescence lifetime imaging microscopy. (1st December 2018)

• Record Type: Journal Article
• Authors: Alex, A.; Frey, S.; Angelene, H.; Neitzel, C.D.; Li, J.; Bower, A.J.; Spillman, D.R.; Marjanovic, M.; Chaney, E.J.; Medler, J.L.; Lee, W.; Vasist Johnson, L.S.; Boppart, S.A.; Arp, Z.
• Is Part Of: British journal of dermatology. Volume 179:Number 6(2018)
• Page Start: 1342
• Page End: 1350
• Publication Date: 2018-12-01
• Subjects: Dermatology -- Periodicals; Skin -- Diseases -- Periodicals; 616.5
• DOI: 10.1111/bjd.16992
• Languages: English
• ISSNs: 0007-0963

Abstract

Summary: Background: GSK2894512 is a topically delivered investigational drug being developed for treatment of atopic dermatitis and psoriasis. Objectives: To investigate, in a phase I clinical trial, the spatial biodistribution and residency of GSK2894512 within the epidermis and dermis of healthy human participants noninvasively using fluorescence lifetime imaging microscopy (FLIM). Methods: Two topical drug formulations containing GSK2894512 1% were applied to the right and left forearms of six participants for seven consecutive days, followed by seven days of observation for residency. FLIM images were obtained daily throughout the study, approximately every 24 h. During the treatment phase of the study, images were collected from each participant pretreatment, reflecting the residual dose from the previous day. Three punch biopsies from each participant of one formulation was obtained from the treated region during the post‐treatment follow‐up period between days 8 and 14 for comparison with FLIM results. Results: Cellular and subcellular features associated with different epidermal and dermal layers were visualized noninvasively, down to a depth of 200 μm. Results yielded three‐dimensional maps of GSK2894512 spatial distribution and residency over time. This fluorescence data provided a marker that was used as a monitor for day‐to‐day variance of drug presence and residency postapplication. Conclusions: The results suggest FLIM could be a viable alternative to skin biopsies without the usual patient discomfort and limitations, thereby enabling the direct measurement of skin distribution through longitudinal monitoring. These results are the first step in establishing the unique capabilities that multiphoton imaging could provide to patients through noninvasive drug detection.