Targeted cutaneous delivery of etanercept using Er:YAG fractional laser ablation

The aim was to investigate the feasibility of using Er:YAG fractional laser ablation to enable topical cutaneous delivery of etanercept (ETA). Preliminary investigations into the effect of fluence on micropore depth, measured by full-field optical coherence tomography, were followed by quantitative experiments to determine ETA delivery and its cutaneous biodistribution from solution and hydrogel formulations. Visualization studies were performed using confocal laser scanning microscopy and an ETA-fluorescein conjugate. Micropore depth was linearly dependent on laser fluence. However, use of a single pulse or pulse stacking (i.e. multiple pulses) to apply a given fluence affected pore depth; this was accommodated mathematically by including a stacking factor. ETA delivery into porated skin from solution and 0.8% Carbopol (R) formulations was equivalent: increasing ETA content in the gels from 0.5 to 1 and 2% increased ETA delivery linearly (Formulations 7-9: 5.12 +/- 0.95 to 7.48 +/- 1.45 and 11.2 +/- 2.2 mu g/cm(2), respectively; 10% FAA, 89.9 J/cm(2), 5 ppp); occlusion further increased ETA delivery from Formulation 9 to 23.17 +/- 6.62 mu g/cm(2). Cutaneous biodistribution studies demonstrated that ETA was delivered in therapeutically relevant amounts to the epidermis and dermis. Topical laser-assisted delivery of ETA might expand its range of clinical indications to include recalcitrant but not widespread psoriatic plaques (clinical trial underway).