Potential of combined ultrasound and microneedles for enhanced transdermal drug permeation: A review

• Review of combined ultrasound and microneedles for transdermal drug delivery (TDD).
• Time series analyses of the trends of ultrasound and microneedle for TDD conducted.
• Cluster analysis of the significance of the above combined TDD method carried out.
• Cluster analysis suggests good potential of ultrasound and microneedles for TDD.

Transdermal drug delivery (TDD) is limited by the outer layer of the skin, i.e., the stratum corneum. Research on TDD has become very active in the recent years and various technologies have been developed to overcome the resistance of the stratum corneum to molecular diffusion. In particular, researchers have started to consider the possibility of combining the TDD technologies in order to have further increase in drug permeability. Both microneedles (MNs) and ultrasound are promising technologies. They achieve enhancement in drug permeation via different mechanisms and therefore give a good potential for combining with each other. This review will focus on discussing the potential of this combinational technique along with other important issues, e.g., the mechanisms of ultrasound and MNs as it is and these mechanisms which are coupled via the two systems (i.e. MNs and ultrasound). We discuss the possible ways to achieve this combination as well as how this combination would increase the permeability. Some of the undeveloped (weaker) research areas of MNs and sonophoresis are also discussed in order to understand the true potential of combining the two technologies when they are developed further in the future. We propose several hypothetical combinations based on the possible mechanisms involved in MNs and ultrasound. Furthermore, we carry out a cluster analysis by which we determine the significance of this combinational method in comparison with some other selected combinational methods for TDD (e.g., MNs and iontophoresis). Using a time series analysis tool (ARIMA model), the current trend and the future development of combined MNs and ultrasound are also analysed. Overall, the review in this paper indicates that combining MNs and ultrasound is a promising TDD method for the future.

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