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PubMed2006

Skin microcirculatory effect of exogenous calcitonin gene-related peptide (CGRP) evaluated by laser Doppler flowmetry coupled with iontophoresis in healthy subjects.

The aim of our study was to evaluate the feasibility of laser Doppler flowmetry (LDF) coupled with iontophoresis in exploring the skin vasodilator activity of exogenous calcitonin gene-related peptide (CGRP) in healthy subjects and to investigate the mechanisms involved in the skin vasodilator activity of this peptide. Forearm skin blood perfusion was measured in conventional perfusion unit (PU; 1 PU=10 mV), using a LDF apparatus (Periflux PF4001, Perimed, Sweden), before and following exogenous CGRP dissolved in distilled water (0.02%) or pure saline iontophoresis. Different iontophoresis protocols were used in a preliminary dose finding study in six subjects. Two pulses (0.1 mA for 30 s each) of anodal CGRP or saline iontophoresis were used in the definitive study in 20 subjects. Power spectral density (PSD) of skin blood flowmotion frequency intervals (FI), related to endothelial (0.009-0.02 Hz), sympathetic (0.02-0.06 Hz), myogenic (0.06-0.2 Hz), respiratory (0.2-0.6 Hz) and heart (0.6-1.6 Hz) activities, was also measured in PU(2)/Hz, by means of spectral analysis of the skin LDF signal registered before and following iontophoresis of CGRP or saline in the definitive study. A significantly higher per cent increase in skin perfusion compared to baseline was observed following CGRP than saline iontophoresis (548+/-369% vs. 326+/-192%, p<0.05), with higher hyperaemic response to pure saline than CGRP iontophoresis in only five subjects. A significant increase (p<0.05) in PSD mean value of the five FI considered, was also observed following CGRP iontophoresis, while saline iontophoresis elicited a significant increase (p<0.05) only in PSD of the FI related to endothelial, respiratory and heart activity. These findings demonstrated that LDF coupled with iontophoresis is a feasible method in evaluating the vasodilator effect of exogenous CGRP in human skin and suggest that this peptide directly or indirectly induces a smooth muscle vascular cells and sympathetic fibres stimulation.

Adult↗

PubMed2004

Comparison of EMLA and lidocaine iontophoresis for cannulation analgesia.

BACKGROUND AND OBJECTIVE: Eutectic mixture of local anaesthetic cream and lidocaine iontophoresis are effective in providing analgesia for peripheral venous cannulation with small gauge cannulae in adults and children. The objective of this study was to compare the analgesic efficacy of the two techniques directly in patients using larger cannulae. METHODS: In a double-blind, randomized, controlled study we compared the two techniques directly. Twenty-eight patients had the eutectic mixture of local anaesthetic cream applied to the dorsum of one hand for 60 min followed by sham iontophoresis (group EMLA); the other hand had a sham cream applied for 60 min followed by 10 min of 2 mA iontophoresis with lidocaine 4% and epinephrine 1 in 50,000 (group iontophoresis). Within 5 min of completion of iontophoresis an anaesthetist, unaware of treatment allocation, inserted 18-G venous cannulae into veins of both hands. The patient then scored the amount of pain on cannulation using a 10 point verbal rating scale. RESULTS: Eight patients were excluded from analysis due to failed cannulation (two group EMLA, two group iontophoresis), intolerable burning sensation from iontophoresis (one), protocol violation (one), and changes in surgical schedule (two). Pain scores were lower for the EMLA treated hand than for the iontophoresis side (median (range) 1 (0-7) vs. 3 (0-6); P = 0.023). Erythema and paraesthesia were common but short lived on the iontophoresis side. CONCLUSIONS: Although lidocaine iontophoresis is effective more quickly than the eutectic mixture of local anaesthetic cream, the superior quality of analgesia produced by the eutectic mixture in this study should be borne in mind if these treatments are used electively.

Adult↗

PubMed2003

Delivery of antisense oligonucleotide to the cornea by iontophoresis.

We wished to evaluate the potential of iontophoresis to promote the delivery of antisense oligonucleotides (ODN) directed at the vascular endothelial growth factor (VEGF)-R2 receptor (KDR/Flk) to the cornea of the rat eye. Fluorescence (CY5)-labeled ODNs in phosphate-buffered saline (PBS) (20 microM) were locally administered to rat eyes, and their fate within the anterior segment was studied. Thirty-four male, 5-week-old Wistar rats were used for all experiments. The rats were divided in four groups. In group I (12 rats, 12 eyes), the ODNs (20 microM) were delivered by iontophoresis (300 microA for 5 minutes) using a specially designed corneal applicator. In group II (12 rats, 12 eyes), the ODNs (20 microM) were delivered using the same applicator, but no electrical current was applied. In group III (6 rats, 6 eyes), a corneal neovascular reaction was induced prior to the application of ODNs (20 microM), and iontophoresis electrical current was delivered as for group I rats. Group IV (4 rats, 4 eyes) received ODN (60 microM) iontophoresis application (300 microA for 5 minutes) and were used for ODN integrity studies. The animals were killed 5 minutes, 90 minutes, and 24 hours after a single ODN application and studied. Topically applied ODNs using the same iontophoresis applicator but without current do not penetrate the cornea and remain confined to the superficial epithelial layer. ODNs delivered with transcorneoscleral iontophoresis penetrate into all corneal layers and are also detected in the iris. In corneas with neovascularization, ODNs were particularly localized within the vascular endothelial cells of the stroma. ODNs extracted from eye tissues 24 hours after iontophoresis remained unaltered. The iontophoresis current did not cause any detectable ocular damage under these conditions. Iontophoresis promotes the delivery of ODNs to the anterior segment of the eye, including all corneal layers. Iontophoresis of ODNs directed at VEGF-R2 may be used for the design of specific antiangiogenic strategy in diseases of the cornea.

Animals↗

PubMed2005

Cutaneous side-effects of transdermal iontophoresis with and without surfactant pretreatment: a single-blinded, randomized controlled trial.

BACKGROUND: Iontophoresis, a method that facilitates drug transport across skin by an external electrical field, offers the possibility for long-term transdermal delivery of compounds in a well-controlled manner. In general, the literature supports the contention that iontophoresis is a safe procedure. However, there are important medical issues concerning the epidermal and dermal effects of iontophoresis that have not been extensively investigated. Specific and strictly controlled studies on the dermal effect of iontophoresis are scarce. OBJECTIVES: The aim of this study was to investigate the cutaneous side-effects of transdermal iontophoresis application in healthy human volunteers. METHODS: This was a single-blinded, randomized and parallel design study. In one group (n=12) subjects were treated nonocclusively with a surfactant formulation followed by iontophoresis (3-h application at a current density of 250 microA cm(-2)). In another group (n=12) iontophoresis alone was performed. No drug was included in these studies. The corresponding passive treatments served as controls. Noninvasive methods including sensation record, transepidermal water loss (TEWL), skin colour and the visual scoring were used to assess cutaneous effects. RESULTS: Tingling and itching were commonly experienced in the first 30 min of the current application. Iontophoresis in combination with the pretreatment induced significant increases in TEWL values and in skin redness, and resulted in slight to mild erythema and oedema compared with the control. Compared with the iontophoresis alone, the presence of surfactant pretreatment caused slightly more skin irritation (erythema and oedema) but did not further disturb the skin barrier function. CONCLUSIONS: The transdermal iontophoresis challenges the skin barrier function and induces transient mild skin irritation, but does not cause any permanent damage to the skin when applied for 3 h at a current density of 0.25 mA cm(-2).

Adult↗

PubMed1995

[The effect of iontophoresis with several Ca channel blockers for PHN patients].

We performed iontophoresis with Ca channel blockers for healthy adult volunteers. In this clinical study, we used iontophoresis with Ca channel blockers. Ten out patients with PHN treated at our pain clinic were treated with iontophoresis. They were randomly assigned to one of the following four treatments: (1) 5 ml of 4% lidocaine HCl, (2) 2 mg of nicardipine HCl + 5 ml of distilled water, (3) 2 mg of verapamil HCl + 5 ml of distilled water, and (4) 2 mg of diltiazem HCl + 5 ml distilled water. Iontophoresis was performed using the above four drugs on the positive pole. Using a VAS, each patient was evaluated concerning the analgesic effect. The pain before treatment (10 points) was used as the base line. Compared with the scores before treatment, VAS scores decreased significantly after iontophoresis in all four groups. In the lidocaine group, a significant decrease in VAS scores occurred immediately after iontophoresis and lasted up to 24 hours, reaching the nadir at 2 hours. In the nicardipine group, the decrease occurred immediately after iontophoresis and lasted up to one day, reaching the nadir at four hours. In the verapamil group, the decrease started 1 hour after iontophoresis and lasted up to 48 hours, reaching the nadir at 8 hours. In diltiazem group, the decrease started 1 hour after iontophoresis and lasted up to 48 hours, reaching the nadir at 4 hours. Iontophoresis with Ca channel blockers produced a prolonged analgesic effect in PHN patients. Previously we had observed the same effect in adult volunteers. Therefore, we believe that this therapy will be clinically useful.

Aged↗

PubMed2002

The effect of aspirin and various iontophoresis solution vehicles on skin microvascular reactivity.

The two main objectives of this study were: (1) to examine the effect of aspirin on the endothelial function in healthy subjects and (2) to examine the effect of deionized water and 5% NaCl as iontophoresis solution vehicles. The skin microcirculation was evaluated at the forearm level of healthy subjects. A laser Doppler scanner was employed to measure vasodilation in response to the iontophoresis of 1% acetylcholine (endothelium-dependent) and 1% sodium nitroprusside (endothelium-independent). In the first experiment, nine healthy subjects were given 500 mg aspirin daily for 3 days. The microvascular reactivity was measured at the beginning and the end of the study. In the second experiment, the response to iontophoresis of acetylcholine and sodium nitroprusside as 1% solutions of deionized water was compared to the responses that were achieved after the iontophoresis of deionized water or 5% NaCl solution. After 3 days of aspirin intake, there were no changes in the vasodilatory response to acetylcholine (endothelium-dependent vasodilation) [81 +/- 11 vs 77 +/- 10 (% of increase over baseline at the beginning vs the end of the study, mean +/- SE), P = NS] or sodium nitroprusside (endothelium-independent vasodilation) (69 +/- 8 vs 64 +/- 12, P = NS). There was also a negligible response after the iontophoresis of 5% NaCl (3 +/- 4) and deionized water (6 +/- 4) in anodal mode (the mode employed for the iontophoresis of acetylcholine). In cathodal mode, employed for the iontophoresis of sodium nitroprusside, the response to 5% NaCl was still negligible but a considerable response was found after the iontophoresis of deionized water. In normal healthy subjects, aspirin administration has no effect on forearm skin microvascular reactivity, including both endothelium-dependent and endothelium-independent vasodilation. In addition, a NaCl solution would be preferable to deionized water as the iontophoresis solution vehicle.

Acetylcholine↗

PubMed2004

Iontophoresis-gentamicin delivery into the rabbit cornea, using a hydrogel delivery probe.

PURPOSE: To evaluate the efficacy of penetration of gentamicin into the cornea of rabbits using iontophoresis with a hydrogel-gentamicin containing probe. METHODS: Eight of 10 groups (groups 3-10) of 6 rabbits (one eye per rabbit), underwent corneal iontophoresis using soft stable hydroxyethyl methacrylate hydrogel discs (80% water content) loaded with gentamicin sulphate which were mounted on an iontophoresis probe. The studied current intensities were 0, 0.1, 0.3 and 0.6 mAmp, and the durations of iontophoresis were 10 and 60 sec. Two control groups received 1.4% topical drops of gentamicin every 5 min for 1 hr (group 1) or sub-conjunctival injection of 10 mg gentamicin (group 2). Following sacrifice, aqueous humour was taken, corneas were excised, and gentamicin concentration was determined in aqueous humour and cornea samples. RESULTS: Post-iontophoresis, the concentration of gentamicin in the corneas ranged from high (88.60 +/- 38.64 microg ml(-1)) to very low (0.10 +/- 0.89 microg ml(-1)). Both the control groups and those rabbits treated with current intensity of 0.1 mAmp or greater obtained therapeutic gentamicin levels in the corneas. Use of iontophoresis for 60 sec or current intensity greater than 0.1 mAmp obtained corneal gentamicin levels not different from sub-conjunctival injection. Application of current intensity of 0.1 mAmp or greater gave corneal gentamicin concentrations comparable to topical application of the drug, except when 0.6 mAmp were used for 60 sec (p = 0.05). Increasing current intensity or duration of iontophoresis significantly increased (p = 0.001 for both) gentamicin penetration into the cornea. Current intensity had more influence (Beta2 = 0.40) than duration (Beta2 = 0.13) on drug penetration. A significant interaction was found between the duration of iontophoresis and the current intensity. Very small or no concentrations of the drug were discovered in the anterior chambers of rabbits. CONCLUSIONS: Iontophoresis using hydrogel-gentamicin probe may deliver therapeutic concentrations of gentamicin into the cornea.

Animals↗

PubMed1998

Iontophoresis itself on hairless mouse skin induces the loss of the epidermal calcium gradient without skin barrier impairment.

Iontophoresis increases the delivery of drugs across the stratum corneum, but the pathway by which ionized drugs transit the stratum corneum is unknown. In this study we examined the effect of iontophoresis on the skin barrier and the epidermal calcium gradient. Hairless mice were subjected to iontophoresis for 5-120 min and skin specimens were prepared for electron microscopy. Neither positive nor negative iontophoresis affected transepidermal water loss. Lacunar dilatation and partial distention of the intercellular layers of the stratum corneum were observed in rough proportion to applied time in iontophoresis skin as well as control skin. Additionally, using calcium capture cytochemistry, we demonstrated that both positive and negative iontophoresis caused the disappearance of the epidermal calcium gradient with marked decrease in calcium content in the upper epidermis. Positive iontophoresis was associated with increased calcium in the stratum basale and dermis, whereas negative iontophoresis increased calcium in the stratum corneum. Moreover, as previously shown after barrier disruption and sonophoresis, the decrease in calcium content in the upper epidermis was associated with an increase in lamellar body secretion and the build up of lamellar material at the stratum corneum-stratum granulosum interface. In conclusion, iontophoresis on the skin of hairless mice may induce the change of ionized molecules in the epidermis, as the loss of the calcium gradient, which causes the decrease of skin impedence, gives charged drugs the ability to cross the skin more easily. Also, the structural changes, such as lacunar dilatation, whether they result from hydration or occlusion, may help the transport of charged drugs across the stratum corneum.

Animals↗

PubMed1995

The iontophoresis of fentanyl citrate in humans.

BACKGROUND: Iontophoresis is a method of transdermal administration of ionizable drugs in which the electrically charged components are propelled through the skin by an external electric field. This study was designed to determine whether iontophoresis could be used to deliver clinically significant doses of fentanyl in humans and whether there is a charge-dose relation in the delivery of fentanyl by iontophoresis. METHODS: Five adult volunteers were tested three times on separate days, once receiving passive treatment of 0.0 mA for 2 h (0 mA.min), iontophoresis 1.0 mA for 2 h (120 mA.min), and iontophoresis 2.0 mA for 2 h (240 mA.min) in an open, randomized, crossover design. Respiratory rate, heart rate, blood pressure, and hemoglobin oxygen saturation were monitored throughout the study. Plasma fentanyl concentrations were measured several times before, during, and after iontophoresis. Plasma fentanyl concentrations were measured by radioimmunoassay. RESULTS: No fentanyl was detected after passive (0.0-mA) fentanyl delivery. The following results were obtained for the 1.0- and 2.0-mA deliveries, respectively. Mean times to detectable concentrations of plasma fentanyl were 33 and 19 min; mean times to maximum concentration were 122 and 119 min; maximum concentrations were 0.76 and 1.59 ng/ml (P = 0.010); mean areas under the curve of the plasma fentanyl concentration versus time relation were 233 and 474 ng.ml-1.min (P = 0.003); and mean elimination half-lives were 354 and 413 min (P = 0.326). Only minor adverse side effects related to iontophoresis occurred. However, typical opioid-related effects occurred frequently in the 1.0- and 2.0-mA administration groups. CONCLUSIONS: Clinically significant doses of fentanyl can be administered by iontophoresis for delivery periods of 2 h. A charge-dose relation exists after administration with currents of 1.0 and 2.0 mA. Future research into the iontophoresis of fentanyl as a method of potent opioid administration is indicated.

Adult↗

PubMed1990

Regional ocular gentamicin levels after transcorneal and transscleral iontophoresis.

Transcorneal and transscleral iontophoresis were compared to subconjunctival injection (control) in the delivery of gentamicin into rabbit eyes. Gentamicin levels in the corena, aqueous, and vitreous were measured by a fluorescence polarization assay at various time intervals after treatment. A mean peak corneal concentration of 376.1 micrograms/ml was achieved 2 hr after transcorneal iontophoresis. This was significantly higher than the level obtained in control eyes (P = 0.016). A mean peak aqueous humor concentration of 54.8 micrograms/ml occurred 2 hr after transcorneal iontophoresis. This was significantly higher than the peak level of 14.2 micrograms/ml after subconjunctival injection (P = 0.003). Inhibitory levels (approximately 5 micrograms/ml) were maintained in both aqueous and cornea for 8 hr after transcorneal iontophoresis. After transscleral iontophoresis, the mean peak vitreous humor concentration was 53.4 micrograms/ml at 16 hr and remained inhibitory through 24 hr; the peak aqueous level was 23.2 micrograms/ml and remained inhibitory for 24 hr. Peak drug concentrations in the vitreous were significantly higher than control (P = 0.026). Therapeutic vitreous humor levels were not achievable after transcorneal iontophoresis or subconjunctival injection. Potential corneal toxicity of transcorneal iontophoresis was demonstrated by measuring corneal thickness and endothelial cell counts prior to and 3 days after transcorneal iontophoresis of gentamicin and balanced saline solution (BSS) (control). No significant differences existed between eyes treated with gentamicin compared to those treated with BSS or when pre- versus postiontophoresis of gentamicin in the same eyes were compared. Transcorneal and transscleral iontophoresis may be an effective noninvasive method of delivering inhibitory levels of gentamicin to the cornea, aqueous humor, and vitreous for the treatment of intraocular infections.

Animals↗

PubMed2005

The influence of iontophoresis on acyclovir transport and accumulation in rabbit ear skin.

PURPOSE: The aim of this work was to explore the effect of iontophoresis on acyclovir (ACV) accumulation and permeation. In particular, the objectives were to check the efficacy of the transport mechanisms, electromigration and electrosmosis, on drug accumulation. METHODS: Permeation experiments were performed in vitro, using rabbit ear skin as barrier, from donor solutions at pH 3.0, 5.8, and 7.4. At the end of the experiments, drug accumulation in epidermis and dermis was measured. Anodal and cathodal iontophoresis were applied at pH 3.0, whereas only anodal iontophoresis was used at pH 5.8 (current densities 0.06--0.50 mA/cm(2)) and 7.4. RESULTS: Cathodal iontophoresis was more efficient than anodal iontophoresis on ACV permeation across the skin at pH 3.0. At pH 5.8, ACV flux and accumulation increased with current density during anodal iontophoresis. At pH 7.4, anodal iontophoresis produced a remarkable increase of flux and a modest increase of accumulation. Overall, anodal flux increased as the pH of the donor solution was increased as a result of the increase of the skin net negative charge. CONCLUSIONS: From the results obtained in the present work, it can be concluded that iontophoresis application increases ACV flux and, to a limited extent, accumulation in the skin.

Acyclovir↗

PubMed2006

Facilitated skin penetration of lidocaine: combination of a short-term iontophoresis and microemulsion formulation.

The objective of this study was to demonstrate the potential of the application of a short-term iontophoresis on the topical delivery of lidocaine hydrochloride from a microemulsion-based system. Five- and 10-min durations of anodal iontophoresis applied onto porcine skin were examined in combination with a microemulsion containing 2.5% lidocaine hydrochloride. A similar combination (10-min iontophoresis with microemulsion in the anodal electrode) was also examined in vivo in a rat model. It was shown in vitro that by combining microemulsion application with a 10-min iontophoresis of 1.13 mA/cm2 electric current density, a significantly increased flux was obtained compared with a combination of aqueous drug solution with the same iontophoresis protocol. In vivo studies revealed that 57.71 +/- 18.65 and 18.43 +/- 9.17 microg cm(-2) were reached in the epidermis and dermis, respectively, at t = 30 min of microemulsion application, when iontophoresis was applied for 10 min. In contrast, the application of aqueous solution-iontophoresis resulted in a relatively lower drug accumulation (21.44 +/- 10.42 and 5.30 +/- 2.25 microg cm(-2) in the epidermis and dermis, respectively, at t = 30) with more rapid clearance of the drug from the skin. Ten-minute application of a low-current electric field on a new topical microemulsion appears to make significant changes in skin permeability. The potential advantages of this procedure include significantly increased flux, accumulation of a large skin drug depot, short lag times, reduced irritation (compared to long-term iontophoresis), simplicity and ease of compliance.

Anesthetics, Local↗

PubMed2004

Reducing pain in ED patients during lumbar puncture: the efficacy and feasibility of iontophoresis, collaborative approach.

INTRODUCTION: This study examined the efficacy and feasibility of a collaborative iontophoresis procedure for dermal anesthesia prior to lumbar puncture (LP) in adult ED patients. METHODS: Patients were randomized to receive lidocaine by iontophoresis or needle infiltration. Emergency nurses and physicians completed a collaborative LP procedure in those randomized to iontophoresis. Usual care was provided for needle infiltration subjects. Pain was assessed at 3 points using an 11-point numeric rating scale to measure pain, and provider satisfaction was recorded. RESULTS: Ninety subjects completed the protocol: infiltration group (n = 48) and iontophoresis group (n = 42). Subjects in the lidocaine infiltration group reported significantly more pain (mean, 4.1A+/-2.6) than subjects in the iontophoresis group (mean, 0.9A+/-1.6) ( t82 = 1.26, P =.000). There was no significant difference between the pain experienced during the lumbar puncture by both groups. Mean pain score during LP was 3.7 (+/-2.7) for iontophoresis compared to 3.4 (+/-2.9) for infiltration. More iontophoresis subjects (18 or 43.9%) required "rescue" lidocaine than infiltration subjects (12 or 24.5%) (chi-square 1 =3.79, P =.0515). Providers reported greater satisfaction with the collaborative procedure compared to physician administered lidocaine infiltration and anecdotally reported that iontophoretic anesthesia administration does not obscure anatomical landmarks, as needle infiltration can. Time for completion of dermal anesthesia using the iontophoretic procedure was longer than time for completion of dermal anesthesia using the lidocaine infiltration procedure (12A+/-12 min vs 2A+/-1.7 min); however, no statistically significant difference in total LP time or ED length of stay was found. NURSING IMPLICATIONS: Dermal anesthesia by lidocaine iontophoresis in patients undergoing an LP with emergency nurses and physicians working in collaboration during the procedure takes longer, but decreases the pain of administering anesthesia, increases provider satisfaction, and fosters collaborative practice in the emergency setting. Iontophoretic administration of anesthesia for LP is now an option for dermal anesthesia in our emergency department.

Adolescent↗

PubMed2003

Nonspecific vasodilatation during transdermal iontophoresis-the effect of voltage over the skin.

We used laser Doppler perfusion imaging (LDPI) to study nonspecific vasodilatation during iontophoresis. In iontophoresis studies, nonspecific vasodilatation occurs as a result either of galvanic currents or of the applied voltage over the skin. We made dose-response measurements to study the effect of ionic strength of the vehicle on the nonspecific vasodilatation during iontophoresis of sodium chloride and deionized water, while we monitored the voltage over the skin. We found that anodal and cathodal ionotophoresis induced a voltage over the skin that was dependent on the ionic strength of the test solution. The nonspecific vasodilatation during anodal iontophoresis was less pronounced than during cathodal iontophoresis, and was independent of the voltage over the skin. The nonspecific vasodilatation in cathodal iontophoresis was related to the voltage over the skin, and was possibly mediated by depolarization of local sensory nerves. In experiments using cathodal iontophoresis, therefore, the ionic strengths of the vehicle and the drug are important when vasoactive drugs are examined, as the nonspecific vasodilatation needs to be controlled for. As the vasodilatation that we observed was heterogeneously distributed within the area of iontophoresis, LDPI may provide more accurate measurements than conventional laser Doppler perfusion monitoring.

Administration, Cutaneous↗

PubMed2002

Transdermal iontophoresis of sodium nonivamide acetate. V. Combined effect of physical enhancement methods.

The effect of iontophoresis combined with treatment of other physical enhancement methods such as electroporation, low frequency ultrasound, and erbium:YAG (yttrium-aluminum-garnet) laser on the transdermal delivery of sodium nonivamide acetate (SNA) was examined in this present study. Iontophoresis increased the transdermal flux of SNA in vitro as compared to the passive diffusion without any enhancement. Furthermore, iontophoresis was always the most potent enhancement method for SNA permeation among the physical enhancement methods tested. Pulsing of high voltages (electroporation) followed by iontophoresis did not result in increased transport over iontophoresis alone. However, electroporation shortened the onset of transdermal iontophoretic delivery of SNA. Pretreatment of low frequency ultrasound (sonophoresis) alone on skin did not increase the skin permeation of SNA. The combination of iontophoresis and sonophoresis increased transdermal SNA transport more than each method by itself. The enhancement of drug transport across shunt routes and reduction of the threshold voltage in the presence of an electric field may contribute to this synergistic effect. Use of an erbium:YAG laser was a good method for enhancing transdermal absorption of SNA because it allows precise control of stratum corneum (SC) removal, and this ablation of SC could be reversible to the original normal status. The combination of laser treatment and iontophoresis also synergized the skin permeation of SNA, possibly due to a gradual drop in the electric resistance of the skin. The results in this present study point out that the choice of certain conditions with suitable physical enhancement methods can induce a synergistic effect on transdermal delivery of SNA during iontophoresis.

Administration, Cutaneous↗

PubMed1998

Characterization of the transport pathways induced during low to moderate voltage iontophoresis in human epidermal membrane.

This report describes the results of iontophoresis experiments involving the transport of polar nonelectrolytes across human epidermal membrane (HEM) at a moderate applied voltage of 2.0 V and where the data are interpreted via a convective transport model and hindered transport theory. A principal finding is that although HEM iontophoresis at 2.0 V resulted in a large increase in HEM porosity, the pore radii of the newly induced pores in HEM as calculated from the iontophoresis data using the hindered transport theory were found to be in the range of 6-12 A. This supports the view that electroporation at these modest applied voltages results in pores with sizes the same order of magnitude but somewhat smaller than those estimated for the preexisting pores in HEM prior to electroporation. This outcome is also important from a practical standpoint, as flux enhancement for large molecules (such as oligonucleotides and polypeptides) arising from electroporation under these conditions would be expected to be significantly less than if the resulting pore sizes were much greater. Providing a "prepulse" of 4.0, 8.0, and 15 V prior to the 2.0 V iontophoresis generally gave greater increases in HEM conductance (and, therefore, in porosity) but did not significantly change the deduced effective pore radii (around 5-9 A). The alteration during and the recovery of HEM after iontophoresis was also investigated. The recovery behavior was found to be dependent upon both the duration of the applied voltage and the magnitude of its effects: the recovery for a HEM sample that experienced a large increase in electrical conductance during iontophoresis was generally poorer than that for a sample that was more resistant to the electric field. Incomplete recovery was generally observed in experiments with long iontophoresis duration (50 min) and with the higher voltages (4.0, 8.0 V, and 15 V). In these cases, the barrier properties of HEM were more greatly altered as indicated by larger increases in the electrical conductance and passive permeability of HEM after iontophoresis.

Biological Transport↗

PubMed2000

Iontophoresis of nickel elicits a delayed cutaneous response in sensitized individuals that is similar to an allergic patch test reaction.

Wearing of patch test chambers for 1-2 days is uncomfortable for patients. Allergen application by iontophoresis avoids this, but it is unknown so far whether iontophoresis itself interferes with the delayed immune response. We compared the effects occurring 48 h after iontophoresis with distilled water, 0.9% NaCl, and 0.01 M NiSO4 in normal volunteers and in nickel-sensitized patients (total n=36). Visual assessment was performed and transepidermal water loss (TEWL), stratum corneum hydration, cutaneous blood flow, and immunohistopathology were determined. After iontophoresis with nickel sulfate, only individuals sensitized to nickel reacted with a positive clinical response, increase in cutaneous blood flow, decline in epidermal CD-1a-positive cells, increase in epidermal proliferation (Ki-67-positive cells), pronounced infiltration of cells positive for CD4, CD11, or CLA, and cellular activation (expression of ICAM1, HLA-DR). Iontophoresis with distilled water or saline did not result in such reactions in volunteers with or without nickel sensitization, and the latter also tolerated nickel iontophoresis without significant skin reactions. We conclude that the delayed cutaneous response to nickel induced via iontophoresis is specific and similar to a positive patch test reaction. Iontophoresis may therefore be considered as an alternative to patch testing.

Adult↗

PubMed2002

Lidocaine iontophoresis versus eutectic mixture of local anesthetics (EMLA) for IV placement in children.

UNLABELLED: Pain during venipuncture is a major source of concern to children and their caretakers. Iontophoresis is a novel technique that uses an electrical current to facilitate movement of solute ions (lidocaine) across the stratum corneum barrier to provide dermal analgesia. In this study, we compared dermal analgesia provided by lidocaine iontophoresis and eutectic mixture of local anesthetics (EMLA). After informed consent, 26 children, aged 7-16 yr, who required venous cannulation on multiple occasions, were enrolled in this prospective, randomized, crossover study to receive EMLA and iontophoresis on separate occasions. During a third session, each subject received his or her preferred treatment. Pain during venipuncture was assessed by the subject, parent, observer, and technician performing the procedure, by use of a 100-mm visual analog scale. The observer also used the Children's Hospital of Eastern Ontario Pain Scale to rate the subject's pain. Ratings of subject satisfaction were also assessed. There were no significant differences between the two groups in the subject-rated visual analog scale or the Children's Hospital of Eastern Ontario Pain Scale scores. Eleven (50%; 95% confidence interval [CI], 31%-69%) of the 22 subjects who completed both sessions preferred iontophoresis. Five subjects (23%; 95% CI, 10%-44%), including two who did not tolerate treatment with iontophoresis, preferred EMLA, and six (27%; 95% CI, 13%-48%) had no preference for the intervention to provide dermal analgesia. We conclude that lidocaine iontophoresis provides similar pain relief for insertion of IV catheters as EMLA and is a useful noninvasive alternative to establish dermal analgesia for venous cannulation. IMPLICATIONS: Iontophoresis is a technique that uses an electrical current to facilitate movement of solute ions (lidocaine) across the stratum corneum barrier to provide dermal analgesia. Lidocaine iontophoresis provides similar pain relief for insertion of IV catheters as eutectic mixture of local anesthetics and is a useful noninvasive alternative to establish dermal analgesia for venous cannulation.

Administration, Topical↗