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Expert Opin Drug Deliv. 2014 Mar;11(3):393-407. doi: 10.1517/17425247.2014.875528. Epub 2014 Jan 7.

Skin permeabilization for transdermal drug delivery: recent advances and future prospects.

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Massachusetts Institute of Technology, Department of Chemical Engineering , Room 76-661, 77 Massachusetts Avenue, Cambridge, MA 02139 , USA +1 617 253 3107 ; +1 617 258 8827 ;



Transdermal delivery has potential advantages over other routes of administration. It could reduce first-pass metabolism associated with oral delivery and is less painful than injections. However, the outermost layer of the skin, the stratum corneum (SC), limits passive diffusion to small lipophilic molecules. Therefore, methods are needed to safely permeabilize the SC so that ionic and larger molecules may be delivered transdermally.


This review focuses on low-frequency sonophoresis, microneedles, electroporation and iontophoresis, and combinations of these methods to permeabilize the SC. The mechanisms of enhancements and developments in the last 5 years are discussed. Potentially high-impact applications, including protein delivery, vaccination and sensing are presented. Finally, commercial interest and clinical trials are discussed.


Not all permeabilization methods are appropriate for all applications. Focused studies into applications utilizing the advantages of each method are needed. The total dose and kinetics of delivery must be considered. Vaccination is one application where permeabilization methods could make an impact. Protein delivery and analyte sensing are also areas of potential impact, although the amount of material that can be delivered (or extracted) is of critical importance. Additional work on the miniaturization of these technologies will help to increase commercial interest.

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