Electroporation, transdermal drug

Prausnitz, M.R., et al. 1993. Electroporation of mammalian skin A mechanism to enhance transdermal drug delivery. Proc Natl Acad Sci USA 90 10504. 

Prausnitz, M.R. 1999. A practical assessment of transdermal drug delivery by skin electroporation. 

Pliquett, U. 1999. Mechanistic studies of molecular transdermal transport due to skin electroporation. Adv Drug Deliv Rev 35 41. 

Ointments, creams, and plasters are used for transdermal drug delivery. In the latter case, sustained release is accomplished by diffusion from a reservoir through a microporous membrane and into the skin [26,48,49]. Iontophoresis and electroporation has been reported to successfully promote transdermal delivery rates [50-52]. 

Weaver JC. Electroporation A general phenomenon for manipulating cells and tissues. J. Cell Biochem. 1993 51(4) 426-435. Prausnitz MR. A practical assessment of transdermal drug delivery by skin electroporation. Adv. Drug Deliv. Rev. 1999 35 61-76. Edwards DA, Prausnitz MR, Danger R, and Weaver JC. Analysis of enhanced transdermal transport by skin electroporation. J. Control. Rel. 1995 34 211-221. 

The present summary will cover only those technologies where the drug formulation itself is used to penetrate the skin via its mechanical energy. It will not describe any technology where a needle is used to puncture the skin, even if the needle is not visible to the patient or only the epidermis is punctured, such as mini-needles, microneedles, pen injectors, or autoinjectors. Also excluded are systems that ablate the skin mechanically or otherwise disrupt its chemical or mechanical structure to increase its permeability, such as laser ablation, microdermal ablation, electroporation, or iontophoresis. These are usually referred to as transdermal drug delivery, but can also be described as needle free. 

Inovio Biomedical Corporation (San Diego, CA) have developed a prototype electroporation transdermal device, which has been tested with various compounds with a view to achieving gene delivery, improving drug delivery and aiding the application of cosmetics. Other transdermal devices based on electroporation have been proposed by various groups [38 1] however, more clinical information on the safety and efficacy of the technique is required to assess the future commercial prospects. 

Wong, TW, Chen, C.H., Huang, C.C., Lin, C.D. and Hui, S.W. (2006) Painless electroporation with a new needle-free microelectrode array to enhance transdermal drug delivery . J. Control. Release. 110(3), 557-565. 

During electroporation, cells or tissues are exposed to an electric field with high voltage (up to 1 kV). Short, rapid pulses cause transient membrane instability and the formation of pores with a mean lifetime of minutes [30]. Soluble DNA constructs that have been added to the culture medium or injected into the tissue may thereby enter the cell and ultimately reach the nucleus. The basic principle is also known to pharmacists as iontophoresis and is used for transdermal drug apphcation [31]. This gene transfection method has so far been well accepted by patients and is safe, especially due to the low risk of infection. To date, mainly liver, muscle, and skin cells have been transformed this way, mostly via the transdermal route [32]. 

Yan K., Todo H., Sugibayashi K. (2010). Transdermal drug delivery by in-skin electroporation using a microneedle array. 

Transdermal drug delivery through iontophoresis has received widespread attention. A long-term delivery with transdermal DC voltage of <5 V was used (Phquett and Weaver, 1996). High-voltage pulses up to 200 V decaying in about 1 ms have also been used on human skin for enhancement of transport by electroporation (Phquett and Weaver, 1996). The effect was found to be due to the creation of aqueous pathways in the stratum corneum. 

Denet A, Vanbever R, Preat V. Skin electroporation for transdermal and topical delivery. Adv Drug Delivery Rev 2004 56 659-674. 

Riviere, J.E., et al. 1995. Pulsatile transdermal delivery of LHRH using electroporation Drug delivery and skin toxicology. J Control Release 40 229. 

Badkar, A.V., et al. 1999. Enhancement of transdermal iontophoretic delivery of a liposomal formulation of colchicine by electroporation. Drug Deliv 6 111. 

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