EX VIVO VISUALIZATION AND EXTENDED DRUG RELEASE FROM A DISSOLVABLE MICROARRAY
K. T. Nielsen, A. H. Eriksson, M. F. Carlsen, K. M. Engell, J. Jansson, K. Petersson, M. A. Røpke, M.Bertelsen, P. Kemp
LEO Pharma A/S, Ballerup, Denmark
The aim of the study was to investigate a dissolvable microarray (MA) patch in terms of skin insertion and drug release in the human NativeSkin® model for 6 days and in vivo using minipigs for 4 days.
The patches contain polymeric, microscopic arrays composed of a fast dissolving drug-free backing layer and slowly dissolving drug containing tips. The calcipotriol and betamethasone dipropionate (BDP) is encapsulated in the tip and delivered in a pain-free and minimally invasive manner by micro-perforation of the stratum corneum with 500 µm long microneedles. In the skin the drug will be slowly released thereby making it possible to reduce the dosing frequency.
MA needles were visualized by Scanning Electron Microscopy (SEM) and skin penetration was studied using reflectance confocal microscopy (RCM). To study the extent and duration of drug release from the MAs, a single application of a patch was compared in the human NativeSkin® model (Genoskin, France) from three healthy donors and in vivo to daily application of a gel containing the same active pharmaceutical ingredients.  Drug release was assessed at several time points after application by quantifying target engagement (TE) biomarkers and drug metabolism reflecting free drug available in the viable skin. Thus, calcipotriol release was assessed by quantifying the Vitamin D (VitD) TE biomarkers CYP24A1 and CD14 by qPCR, and BDP release was assessed through quantification of a BDP metabolite.
RCM showed efficient penetration of the MA patches into the upper dermis. The observed VitD TE biomarkers and BDP metabolite levels were similar for a single applied MA patch compared to daily treatment with the comparator, Daivobet® gel for up to 6 days in the human NativeSkin® model and up to 4 days in minipigs.
Studies on calcipotriol and BDP containing MA patches in human skin explants and Göttingen minipigs showed prolonged VitD target engagement and elevated BDP metabolite levels, on par with once daily application of the comparator Daivobet® Gel. The MA patches may offer a convenient treat-and-go approach with reduced dosing frequency and are currently in Phase 1 clinical development in psoriasis.