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

Abstract

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

Permeation enhancer strategies in transdermal drug delivery

“…Physiochemical properties of the drug delivery system (Rehman & Zulfakar, 2014;Schoellhammer et al, 2014) Release characteristics…”

Transdermal drug delivery: 30 + years of war and still fighting!

“…The number of publications addressing these technologies, especially microneedles, is growing exponentially and recent, authorative reviews are available in the literature [19][20][21][22][23][24]. In each approach, new, aqueous pathways are created across the outer few hundred microns (give or take) of the skin allowing the barrier function of the SC to be 'short-circuited' and relaxing two key limitations of passive transdermal delivery:…”

Imaging the dynamics of individual electropores

“…Since its discovery and the first investigations in the 1960s and 1970s (4,5), electroporation has been used in a wide range of applications, including gene transfection (6), wound and water sterilization (7,8), tumor ablation (9,10), electrochemotherapy (11,12), and transdermal drug delivery (13). Furthermore, links to defibrillation damage have been highlighted (14).…”