Medicinal electrophoresis: how it works

Drug electrophoresis is a non-invasive application of a weak direct current through the skin to transport charged drug molecules from a soaked pad beneath an active electrode into the superficial tissues, where a local depot is formed and diffusion occurs. This method is considered a controlled method of local delivery, bypassing the stratum corneum and reducing systemic exposure. [1]

The mechanism is based on the movement of ions under the influence of an electric field and the accompanying flow of solvent through the pores and ducts of sweat glands. These processes are described by two mechanisms: electromigration, that is, the repulsion of like charges, and electroosmosis, the volumetric flow of fluid from the anode to the cathode through the charged skin matrix. The balance of these mechanisms depends on the properties of the drug and the environment. [2]

In practice, electrophoresis is considered an adjunct to active rehabilitation rather than a replacement for causal treatment. The clinical value of this method is higher where short-term pain and inflammation reduction is required during exercise and load modification. The evidence base is mixed and shows the greatest benefit in specific scenarios with the correct selection of parameters and polarity. [3]

Table 1. Mechanisms and factors influencing delivery

Parameter	The essence	Practical significance
Electromigration	Repulsion of like charges "drug - active electrode"	Determines the choice of polarity and active electrode
Electroosmosis	Volumetric transfer of water through the skin, usually from the anode to the cathode	Affects the transfer of weak bases and neutral molecules
Solution chemistry	pH, ionic strength, buffer, competing ions	Determines the fraction of ionized form and "current competition"
Area and contact	Size and fit of the pad, moisture	Affect current density and the risk of skin irritation
Electric current dose	Current-time product, typical target 40-80 mA min	Associated with the amount of charge transferred by the ions

Source: Reviews of iontophoresis and modern transdermal delivery. [4]

How it works: the physics of the process and pharmacokinetics

The transport of charged molecules is controlled by an electric field gradient: negative ions are supplied from beneath the cathode, positive ions from beneath the anode. Penetration depth is limited primarily by the dermis and the upper layers of underlying tissue, but a skin "depot" is formed from which the molecules diffuse after the procedure. This ensures a localized, rather than systemic, exposure profile. [5]

Efficiency is affected by the size and charge of the molecule, the pH of the donor solution, the composition of the buffer, the type of electrodes, as well as the current strength and duration of exposure. For anions, competition with chloride released under the silver-chloride cathode is critical, requiring a rational solution formula without mobile co-anions. [6]

The current density is chosen to be safe: traditionally, a limit of approximately 0.5 mA per cm² of active electrode is used to minimize irritation and chemical burns. In clinical settings, the dose is often specified as mA min—for example, 40 mA min at a current of 2 mA for 20 minutes. [7]

Systemic absorption with topical administration is minimal, reducing the risk of systemic side effects compared to oral forms, although this profile requires experimental confirmation for each molecule. Studies on transdermal delivery emphasize the predominantly local action and the sharp increase in the transfer of polar, hydrophilic molecules compared to simple application. [8]

Table 2. Common drugs and choice of active electrode

Substance and purpose	Charge in solution	Active electrode	Comment
Dexamethasone sodium phosphate for anti-inflammatory effect	Negative	Cathode	Competition with chloride ion is possible; a formula without mobile co-anions is preferable
Lidocaine hydrochloride for local anesthesia	Positive	Anode	The transfer during anodic feeding has been well studied
Acetic acid for soft tissue calcifications	Negative	Cathode	Used in research on plantar fasciitis
Salicylates in dermatological problems	Negative	Cathode	Polarity is negative, used in private clinical series

Source: experimental and clinical work on polarity and formulation. [9]

Equipment, electrodes and dosing

A typical system consists of a continuously variable DC power source, an active electrode with a pad soaked in a medicinal solution, and a dispersed electrode that closes the circuit. Quality contact, uniform pad wetting, and stable fixation are important to avoid localized current surges. [10]

Safety is determined primarily by current density: as current density increases, the risk of local irritation and chemical burns increases due to a shift in pH directly beneath the electrode. An alkaline reaction with the formation of sodium hydroxide is possible beneath the cathode, while an acidic reaction is possible beneath the anode, which justifies the requirements for contact and time monitoring. [11]

The dose is controlled in mA min. In practice, ranges of 40-80 mA min are appropriate, depending on the goal and tolerance: for example, 4 mA for 10-20 minutes or 2 mA for 20-40 minutes. The threshold current is limited by calculation based on the area of the active electrode, so as not to exceed the safe density. [12]

For anionic drugs, cathodic feed is used, while for cationic drugs, anodic feed is used. The solution under the active electrode is prepared with the desired pH to maximize ionization of the target molecule and minimize competing ions. This increases the fraction of target transfer per given current dose. [13]

Table 3. Calculation of safe current and dose

Size	Formula and benchmark	Calculation example
Current density	no more than 0.5 mA per cm²	With an area of 6 cm², the maximum current is 3 mA
Electric current dose	current × time, mA min	2 mA x 20 minutes = 40 mA min
Session time	determined by dose and tolerance	10-30 minutes while monitoring sensations
Pole selection	the drug and the active electrode have the same charge	Dexamethasone from under the cathode, lidocaine from under the anode

Source: clinical guidelines on electrotherapy and review publications. [14]

Where the method is useful: evidence base for conditions

In lateral epicondylitis, randomized trials show pain reduction and improved function with dexamethasone iontophoresis, although the effects depend on the current dose, parameters, and concomitant therapy. Systematic reviews indicate benefits as an adjuvant procedure but emphasize the need for standardized protocols. [15]

In plantar fasciitis, early randomized trials demonstrated the superiority of dexamethasone iontophoresis in terms of short-term symptom relief, especially when used in a multimodal regimen with taping. Current trials continue to compare it with shockwave therapy and other methods, demonstrating comparable short-term effects in some patients. [16]

For soft tissue pain syndromes outside the aforementioned nosologies, the data are mixed: there are signs of benefit when polarity and dose selection guidelines are followed, but the quality of the evidence varies. Clinical guidelines for elbow pain emphasize the priority of active therapy, reserving electrophoresis as a supportive tool in individual cases. [17]

In the area of the temporomandibular joint and some dermatological applications, positive clinical observations and case series have been described with the use of corticosteroids and salicylates, but more powerful studies are needed for broad recommendations. Translational reviews indicate increased transport for polar hydrophilic molecules compared to simple application. [18]

Table 4. Evidence map for the use of drug electrophoresis

Nosology	Summary of pain and function	Horizon of effect	Comment on quality
Lateral epicondylitis	Reduced pain, improved function	Short term	RCT, effect depends on dose and protocol
Plantar fasciitis	Rapid relief in some patients	Short term	RCT: Combination with taping enhances the effect
TMJ and local inflammatory syndromes	Signals of benefit	Short term	Case series, limited evidence
Other soft tissue pains	Heterogeneous	Short term	Standardized RCTs are needed

Source: clinical studies and reviews. [19]

Diagnostic use: pilocarpine iontophoresis test

A separate, well-standardized application of electrical current to move a substance through the skin is pilocarpine sweat stimulation for a quantitative sweat chloride test in cystic fibrosis. Iontophoresis lasts 5 minutes, then sweat is collected for up to 30 minutes using a method approved by professional societies. [20]

The Gibson-Cook method and modern sweat collection systems remain the "gold standard" for screening and diagnosis with appropriate preanalysis. Threshold values are interpreted as follows: less than 30 mmol/L is normal, 30-59 mmol/L is the intermediate zone, and 60 mmol/L and above is the diagnostic range. [21]

It is important to distinguish the diagnostic pilocarpine iontophoresis procedure from medicinal electrophoresis: the goals, solutions and areas of action differ, but both methods rely on the same physical principles of ion transfer through the skin. [22]

Table 5. Interpretation of the sweat chloride test

Indicator	Meaning
Norm	less than 30 mmol per l
Border zone	30-59 mmol/L
Diagnostic range	60 mmol/L and above

Source: Clinical guidelines for sweat testing.[23]

Safety, contraindications and adverse reactions

The main risks are related to the skin's reaction to the current: tingling, erythema, and rare chemical burns due to high current density, poor contact, or an overdried pad. An alkaline reaction is possible under the cathode, and an acidic reaction under the anode, which explains why prevention involves monitoring parameters and moisture. [24]

Absolute contraindications include implantable electronic devices in the treatment area and skin integrity under the electrode for a specific drug. Relative restrictions include pregnancy for certain areas, epilepsy, severe dermatoses, and drug allergies. The decision is made individually, taking into account alternatives. [25]

Systemic side effects are rare due to minimal resorption with the local regimen, but may occur if the technique is not followed or polarity is not observed. Safety is enhanced by Ag/AgCl electrodes, correct calculation of current density, and careful patient education. [26]

When using anionic corticosteroids, competition with chloride ions at the cathode must be taken into account, affecting the delivered drug dose and requiring a correct solution formula. This is a pharmaceutical aspect of safety and efficacy. [27]

Table 6. Common problems and prevention

Problem	Probable cause	What to do
Burning sensation under the electrode	Excessive current density, poor contact	Increase area, reduce current, moisten the pad
Skin irritation	pH shift under the cathode or anode	Reduce time, change pole to another drug
No effect	Incorrect polarity, competing ions	Check the charge of the molecule and the composition of the solution
Hyperemia after the procedure	Normal response to current	Explain to the patient, control the duration

Source: Electrotherapy clinical practice guidelines and reviews. [28]

How to perform the procedure

Selection and Goal. Establish a measurable goal, such as a 30% pain reduction on a visual scale, and rule out contraindications. Select the drug, polarity, and zone, and coordinate the course as part of a multimodal plan with exercises and patient education. [29]

Preparation. Cleanse the skin, select an active electrode of the desired area, and soak the pad in fresh solution. Calculate the maximum current so that it does not exceed 0.5 mA per cm² of active electrode. Ensure the pad is securely attached and moist. [30]

Stimulation. Set the current so that the sensations are "noticeable but comfortable," and wait until the desired dose is reached, for example, 40 mA min. Monitor the sensations and skin condition. For anionic preparations, apply from under the cathode; for cationic preparations, from under the anode. [31]

Response assessment. Record parameters and effect after each session; if there is no clinically significant improvement after several visits, discontinue the course and adjust the plan in favor of methods with a strong evidence base. [32]

Table 7. Secure Session Checklist

Step	Checkpoint	Not really
Purpose and contraindications	The goal is measurable, there are no contraindications
Polarity	The polarity of the active electrode corresponds to the charge of the drug
Current density	Does not exceed 0.5 mA per cm²
Dose	40-80 mA min was achieved according to tolerance
Leather	Before and after examination, aftercare recommendations

Source: guidelines and review publications. [33]

Conclusions

Medicinal electrophoresis is a controlled method for local delivery of charged molecules with well-understood process physics and predictable limitations on penetration depth. Its greatest practical value is noted as an adjunctive procedure within a multimodal plan for specific pain conditions, primarily with the correct polarity, current dose, and standardized methodology. Decisions are made individually, taking into account goals, risks, and alternatives. [34]