GSK, Collegeville, PA, U.S.A.
GSK, Bangalore, India.
Br J Dermatol. 2018 Dec;179(6):1342-1350. doi: 10.1111/bjd.16992. Epub 2018 Oct 8.
GSK2894512 is a topically delivered investigational drug being developed for treatment of atopic dermatitis and psoriasis.
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).
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.
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.
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.
GSK2894512 是一种局部递药的在研药物，正在开发用于治疗特应性皮炎和银屑病。
在一项 I 期临床试验中，使用荧光寿命成像显微镜（FLIM）非侵入性地研究 GSK2894512 在健康人体参与者表皮和真皮中的空间分布和驻留情况。
将两种含有 GSK28945121%的局部药物制剂应用于六名参与者的左右前臂，连续七天，然后观察驻留情况七天。在整个研究过程中，每天大约每 24 小时获得一次 FLIM 图像。在研究的治疗阶段，从每位参与者的预处理开始采集图像，反映前一天的残留剂量。在治疗后随访期间（第 8 天至第 14 天），从每个参与者的一种制剂的治疗区域获得三个活检标本，与 FLIM 结果进行比较。
可以非侵入性地可视化与不同表皮和真皮层相关的细胞和亚细胞特征，深度可达 200μm。结果生成了 GSK2894512 随时间的空间分布和驻留的三维图谱。这种荧光数据提供了一个标记，可作为药物存在和给药后驻留的日常变化的监测器。
结果表明，FLIM 可以替代皮肤活检，而无需通常的患者不适和限制，从而能够通过纵向监测直接测量皮肤分布。这些结果是建立多光子成像可以通过非侵入性药物检测为患者提供的独特功能的第一步。
