Laser-induced transient skin disruption to enhance cutaneous drug delivery.

The use of pressure waves (PW) to disrupt the stratum corneum (SC) temporarily is an effective strategy to increase the deposition of drug molecules into the skin. However, given the rather modest outcomes when compared with ablation-assisted drug delivery, its potential has been underestimated. Accordingly, the aim of this study was to examine the impact of Resonant Amplitude Waves (RAWs) on increasing cutaneous delivery. RAW phenomena are triggered by focusing a high-peak-power pulsed laser onto an appropriate transducer structure, under space- and time-controlled resolution. In order to determine the optimal conditions for the generation and use of RAWs, a screening of laser parameters setting and an analysis of different geometries of the impact pattern over diverse materials used as transducers was performed, analyzing the footprint of the RAW waves in an agarose gel. The results obtained were then checked and fine-tuned using human skin samples instead of agarose. Furthermore, ex vivo experiments were carried out to characterize the effect of the RAWs in the cutaneous delivery of diclofenac (DIC) and lidocaine (LID) administered in the form of gels. The application of RAWs resulted in an increased delivery of DIC and LID to the skin, whose intensity was dependent on the composition of the formulation. In fact, the maximum observed for DIC and LID in short-time experiments (39.1 ± 11.1 and 153 ± 16 µg/cm, respectively) was comparable to those observed using ablation-assisted drug delivery under the same conditions. In conclusion, the combination of RAWs with specific formulation strategies is a feasible alternative for the cutaneous delivery of drug candidates when short onset of action is required.