In situ biodistribution and residency of a topical anti‐inflammatory using fluorescence lifetime imaging microscopy

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. What's already known about this topic? Fluorescence lifetime imaging (FLIM) has been used to image noninvasively cellular features in humans. FLIM has demonstrated the potential to monitor morphological and metabolic changes at the subcellular level that occur in patients with skin cancer and atopic dermatitis. Its potential for wider utilization in dermal drug discovery or dermatological disease monitoring has seen limited development. What does this study add? This is a first‐of‐its‐kind clinical study in which FLIM was used to monitor drug distribution and residency. It is a first step in establishing the unique capabilities multiphoton imaging could provide to patients via noninva