Transdermal iontophoresis electroporation

Fang J, Hung C, Fang Y, Chan T. Transdermal iontophoresis of 5-fluorouracil combined with electroporation and laser treatment. Int J Pharm 2004 270 241-249. 

Transdermal iontophoresis involves the application of an electric field across the skin to facilitate (primarily) ionic transport across the membrane. Iontophoresis, it is important to point out, is differentiated from electroporation [14], another electrical approach to enhance transdermal transport, by the low fields employed. Whereas iontophoresis has achieved commercialization, there is (to our knowledge) no active development in progress of a transdermal delivery system employing electroporation. 

Transdermal Electrophoretic (iontophoresis), electroporation, chemical permeation enhancers, prodrugs, ultrasonics ... 

Edwards [105] has extended the macrotransport method, originally developed by Brenner [48] and based upon a generalization of Taylor-Aris dispersion theory, to the analysis of electrokinetic transport in spatially periodic porons media. Edwards and Langer [106] applied this methodology to transdermal dmg delivery by iontophoresis and electroporation. 

Denet A, Ucakar B, Preat V. Transdermal delivery of timolol and atenolol using electroporation and iontophoresis in combination a mechanistic approach. Pharm Res 2003 20 1946-1951. 

In contrast to low-current iontophoresis, which utilizes an electrical driving force to push permeants into and across the skin, electroporation increases transdermal transport primarily... 

Iontophoresis by definition is the process of transport of ions into or through a tissue by the use of an applied potential difference across the tissue [52], Depending on the physicochemical characteristics of a molecular species, electrorepulsion is usually the primary mechanism of transdermal transport for ions, whereas electroosmosis and increased passive diffusion (as a result of the reduced barrier properties) are more prominent for neutral species [53]. In contrast, enhancement in flux for neutral or weakly charged species during electroporation arises predominantly from the reduced barrier properties of the membrane, whereas direct electrorepulsion is usually of secondary importance [25],... 

Jadoul and Preat [56] have also proposed a similar explanation for the lack of synergistic effects on transdermal delivery of domperidone with combined electroporation (1 pulse of 1000 V with a time constant of 4 ms) and iontophoresis (0.4 mA/cm2) despite the fact that iontophoresis was switched on within a few seconds after electroporation. Combined pulsing and iontophoresis also did not improve penetration of sodium nonivamide acetate through nude mouse skin [51], Therefore, when combing the two protocols, it should be more efficient to use a system that delivers current during or immediately after pulsing without delay. 

Prausnitz, M.R., et al. 1996. Transdermal transport efficiency during skin electroporation and iontophoresis. J Control Release 38 205. 

Fang, J.Y., et al. 2002. The effects of iontophoresis and electroporation on transdermal delivery of buprenorphine from solutions and hydrogels. J Pharm Pharmacol 54 1329. 

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]. 

Ultrasound may enhance transdermal transport by inducing skin alteration and active transport (forced convention) in the skin. Various other means of transport enhancement, including chemicals, iontophoresis and electroporation, may enhance transport synergis-tically with US. Thus, the evaluation of the synergistic effect of low-frequency US with chemical enhancers and surfactants for permeation of mannitol revealed that application of US or sodium lauryl sulfate (SLS) alone, both for 90 min, increased skin permeability about 8 and 3 times, respectively. However, the combined use of US and a 1% SLS solution increased the skin permeability 200 times to mannitol [129]. 

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. 

Jadoul, A. Regnier, V. Preat, V. Influence of ethanol and propylene glycol addition on the transdermal delivery by iontophoresis and electroporation. Pharm. Res. 1997, 14, S308-S309. 

The application of high-voltage electrical pulses to the skin (so-called electroporation) is another approach that has also been used to increase peptide delivery across the epidermal barrier. Several reviews of the application of electroporation to increase transdermal delivery have been published within the last few years. Unlike iontophoresis, which employs small currents (0.5mA/cm ) for relatively long periods of time (many minutes to hours), electroporation involves exposure of the skin to relatively high voltages (on the order of 30-100 V imposed across the skin) for rather short times, typically one to several hundred millise-conds.t ... 

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