Electrical barrier, skin

It is, however, likely that any future combinations of the strategies will face challenges, not least of which are potential safety and economic considerations, particularly as the techniques involve prolongation of an electrically compromised skin barrier with all the safety issues that involve. 

It is generally accepted that the stratum comeum represents the primary electrical barrier in skin. Though impedance results vary from subject to subject and from site to site on the same individual, the electrical response of skin can be modeled as a simple RC network. Nonideal behavior is associated with environmental conditions, the hydration of the skin, and the integrity of the stratum comeum. 

To test the irritancy potential of substances, two tests which can reliably distinguish between skin corrosives and noncorrosives are endorsed by the European Centre for the Validation of Alternative Methods (ECVAM). The testing procedures are based on the transcutaneous electrical resistance (TER) measurements of rat skin and on a human skin model. Both test systems [141-145] will be briefly outlined below. Nevertheless, these tests are not suited for the group of mild irritants which do not induce an acute effect on the barrier function. For those substances, new markers need to be evaluated. First results are available for heat shock protein 27 where higher levels were observed in skin models after exposure to mildly irritating chemicals [146, 147]. 

The OECD and EU have developed specific test guidelines for in vitro/ex vivo testing of skin corrosion, the Transcutaneous Electrical Tesistance (TER) Test and the Human Skin Model Test (see Table 4.7). In fact, the EU Annex V, B.40 test guideline includes the two adopted OECD in vitro tests for skin corrosion (TG 430 and 431). OECD has also developed a third test guideline for skin corrosion, the In Vitro Membrane Barrier Test this test guideline has not yet been adopted. 

It is therefore desirable to devise strategies both to enhance the penetration of molecules, which can already breach the skin barricade passively to some extent, and also to widen the spectrum of drug molecules that can penetrate the skin at therapeutically beneficial doses. Many tactics have been utilized to help overcome the barrier function. These include chemical means (e.g., chemical penetration enhancers or entrapment of molecules within lipid vesicles) or physical methods (such as ultrasound, microneedles, or electrical methods). Two important electrical methods are iontophoresis and electroporation. 

The experimental protocol involved three consecutive stages of treatment to the same HEM a first passive permeation stage, which lasted for 3 h, followed by a 2 h electrical treatment period during which electroporation or iontophoresis or both protocols were applied to the skin and finally a second passive stage (2 h) evaluated possible reversibility of skin barrier function following electrical treatment. 

Weaver, J.C., T.E. Vaughan, and Y. Chizmadzhev. 1999. Theory of electrical creation of pathways across skin transport barriers. Adv Drug Deliv Rev 35 21. 

We previously demonstrated that application of a negative electric potential on the skin surface affects the ion gradient in the epidermis and accelerates lamellar body secretion and skin barrier recovery.7... 

Topical application of an ionic polymer forms a diffusion electric double layer on the surface of the skin. We evaluated the effects of topical application of ionic polymers on the recovery rate of the skin barrier after injury. Application of a nonionic polymer did not affect the barrier recovery. Application of sodium salts of anionic polymers accelerated the barrier recovery, while that of cationic polymers delayed it. Topical application of a sodium-exchange resin accelerated the barrier recovery, but application of a calcium-exchange resin had no effect, even when the resins had the same structure. Application of a chloride-exchange resin delayed barrier recovery. Thus, topical application of ionic polymers markedly influenced skin barrier homeostasis (Figure 15.2). 

Barium sulfate is a stable inorganic material that has been used for contrast media or cosmetic products because of its stability. Since a negative external electric potential accelerates skin barrier repair after barrier disruption, we hypothesized that topical application of barium sulfate would affect the skin barrier recovery rate, depending on the f potential. 

Denda, M. and Kumazawa, N., Negative electric potential induces epidermal lamellar body secretion and accelerates skin barrier recovery after barrier disruption. J. Invest. Dermatol. 118 65-72, 2002. 

In order to check for possible leakage of skin membranes, it is recommended to test the integrity. Measnrement of electrical resistance or permeability of tritiated water prior to application of the test compound is the most commonly used method (Lawrence, 1997). For practical reasons, skin is often stored at —20°C prior to use. It has been reported that the barrier function does not alter when skin is appropriately stored and is not repeatedly thawed (Swarbrick et al, 1982). 

Lawrence, J.N. (1997). Electrical resistance and tritiated water permeability as indicators of barrier integrity of in vitro human skin, Toxicol In Vitro, 11, 241-249. 

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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