Visualizing and quantifying drug uptake in skin

The study of drug uptake, distribution, and activity within skin is a necessary but problematic requirement in the development and translation of compounds from the bench to the bedside. Drug delivery into the skin is highly complex, due in part to the natural barrier function of the stratum corneum in addition to the many different routes of transdermal entry of drugs. Moreover, skin is not uniform throughout the body or across age groups. For example, epidermal thickness changes 30-fold from the thick skin of the fingertips (485 m) to the thin skin of the face and eyelids (17 m).1 Transdermal delivery can occur over a wide range of timescales (from seconds to hours), and the number of potential cellular targets necessitates quantification on the micrometer scale.2 Optical imaging tools are well-suited to meet these challenges, in particular for the uptake of drugs within the first millimeter of skin. Fluorescence, Raman, and nonlinear optical imaging techniques offer subcellular resolution, rapid real-time 3D image acquisition, and the ability to quantitatively analyze imaging data for both pharmacokinetic and pharmacodynamic information. Optical tools are unique in that they also offer the ability to quantify drugs via phenomena that emerge from their structure, including light absorption, fluorescence, and molecular vibrations. This is particularly useful as most pharmaceuticals are small molecules, where modification to include a reporter can completely change the behavior and thus uptake of the compound. Fluorescence imaging methods can be particularly powerful in measuring the uptake and distribution of drugs. We have been developing a topical acne gel, BPX-01, that is currently in a clinical Phase 2b dose-finding study. BPX-01 is an anhydrous hydrophilic topical gel with solubilized minocycline for enhanced cutaneous delivery and bioavailability to target Figure 1. Conventional fluorescence microscopy images of ex vivo human facial skin specimens. (a) Control, and those treated with (b) 1% BPX-01 (a topical acne gel) and (c) 4% BPX-01 at 24 hours. Minocycline fluorescence is shown in red.