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Photoacoustic (PA) waves generated by short laser pulses absorbed by piezophotonic materials are shown to permeabilize the stratum corneum to large molecules and proteins. Two minutes of such PA waves at a laser pulse frequency of 20 Hz increase the transepidermal water loss (TEWL) of healthy human skin by a factor of 2.5, and the skin relaxes to normal two minutes later. The intraepidermal delivery of Green Fluorescence Protein (GFP) in minipigs with this method does not lead to observable adverse effects. The distinctive features of the piezophotonic materials are the high light-to-pressure conversion efficiency and the generation of PA waves with the duration of the laser pulses. Such features combine to yield broadband pressure waves with steep pressure gradients that are capable of permeabilizing the stratum corneum.