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PubMed1995

[Transdermal iontophoresis of insulin: effect of penetration enhancers on blood glucose level in diabetic rats].

The effects of many usual penetration enhancers such as azone (AZ), oleic acid (OA), poloxamer 188 (POL 188) and propylene glycol (PG) on the blood glucose level in diabetic rats after transdermal iontophoresis of insulin were studied. The change of blood glucose level (D%), defined as the percent ratio of the concentration of blood glucose in rats after the iontophoretic application of insulin to that before administration of insulin, was used to present the data. The results showed that following iontophoretic application of insulin for 3 h, the D% in diabetic rats treated with 100% AZ and 5% AZ/PG was 38.58% and 25.28% respectively, and the D% in diabetic rats untreated with enhancers was 45.48%. The D% in diabetic rats treated with 100% OA, 10%-OA/PG, 10% POL 188/PG and 100% PG was 66.28%, 60.47%, 76.75% and 57.93% respectively. So, AZ showed a synergistic effect on the ability of iontophoresis to promote skin permeation of insulin, and PG further increased this effect. The combination of AZ, PG and iontophoresis increased the permeation of insulin significantly. OA, POL 188 and PG did not display synergistic effect on iontophoresis enhancement. The combination of iontophoresis and some enhancers provided a novel idea and possibility for the administration of polypeptide drugs.

Administration, Cutaneous↗

PubMed1998

Reduction of corneal edema in endotoxin-induced uveitis after application of L-NAME as nitric oxide synthase inhibitor in rats by iontophoresis.

PURPOSE: To investigate the involvement of the cornea during endotoxin-induced uveitis (EIU) in the rat and the effect of Ngamma-nitro-L-arginine methyl ester (L-NAME) as nitric oxide synthase (NOS) inhibitor, administered by iontophoresis. METHODS: EIU was induced in Lewis rats that were killed at 8 and 16 hours after lipopolysaccharide (LPS) injection. The severity of uveitis was evaluated clinically at 16 hours, and nitrite levels were evaluated in the aqueous humor at 8 hours. Corneal thickness was measured, 16 hours after LPS injection, on histologic sections using an image analyzer. Transmission electron microscopy (TEM) was used for fine analysis of the cornea. Transcorneoscleral iontophoresis of L-NAME (100 mM) was performed either at LPS injection or at 1 and 2 hours after LPS injection. RESULTS: At 16 hours after LPS injection, mean corneal thickness was 153.7+/-5.58 microm in the group of rats injected with LPS (n=8) compared with 126.89+/-11.11 microm in the saline-injected rats (n=8) (P < 0.01). TEM showed stromal edema and signs of damage in the endothelial and epithelial layers. In the group of rats treated by three successive iontophoreses of L-NAME (n=8), corneal thickness was 125.24+/-10.36 microm compared with 146.76+/-7.52 microm in the group of rats treated with iontophoresis of saline (n=8), (P=0.015). TEM observation showed a reduction of stromal edema and a normal endothelium. Nitrite levels in the aqueous humor were significantly reduced at 8 hours by L-NAME treatment (P=0.03). No effect on corneal edema was observed after a single iontophoresis of L-NAME at LPS injection (P=0.19). Iontophoresis of saline by itself induced no change in corneal thickness nor in TEM structure analysis compared with normal rats. CONCLUSIONS: Corneal edema is observed during EIU. This edema is significantly reduced by three successive iontophoreses of L-NAME, which partially inhibited the inflammation. A role of nitric oxide in the corneal endothelium functions may explain the antiedematous effect of L-NAME.

Animals↗

PubMed1976

An isolated current monitor for iontophoresis.

An inexpensive isolated current monitor has been developed as an effort to minimize stimulus artifact in experimental systems which include iontophoresis as the source of stimulus. The monitor becomes an element of the iontophoresis circuit, but provides an output voltage isolated from the iontophoresis current. The voltage is proportional to the iontophoresis current and will represent currents of 1/2 nA to 5 muA. It is this ability to detect minute currents that is valuable in iontophoresis measurements.

Electricity↗

PubMed1982

Single cell responses in cat visual cortex to visual stimulation during iontophoresis of noradrenaline.

We studied how iontophoresis of noradrenaline (NA) changes responsiveness of individual cells in the feline visual cortex when their visual receptive fields are stimulated with the appropriate visual stimulus. We found three populations of cortical cells which either increased, decreased or did not change their visual responsiveness during NA iontophoresis. About equal numbers of cells belonged to each of these three groups. In the majority of such cells that changed visual responsiveness during NA iontophoresis and that had measureable amounts of spontaneous activity, the ratio of visually evoked to spontaneous activity (signal-to-noise ratio) improved during NA iontophoresis. This improvement was independent of the direction of changes in the response magnitude to visual stimulation. There was a differential effect of NA on simple and complex visual cortical cells: Although most simple cells (86%) clearly changed their responsiveness during NA iontophoresis, the effects were seen in only one-third of complex cells. Furthermore, the effects on complex cells were usually weak compared to those typically seen in simple cells. In some cases the effects of NA were more complicated than an overall enhancement of suppression of the cortical cell's responses to visual stimulation. The possible dual role of NA in the visual cortex is briefly discussed.

Animals↗

PubMed2004

Quantitative study of electrophoretic and electroosmotic enhancement during alternating current iontophoresis across synthetic membranes.

One of the primary safety and tolerability limitations of direct current iontophoresis is the potential for electrochemical burns associated with the necessary current densities and/or application times required for effective treatment. Alternating current (AC) transdermal iontophoresis has the potential to eliminate electrochemical burns that are frequently observed during direct current transdermal iontophoresis. Although it has been demonstrated that the intrinsic permeability of skin can be increased by applying low-to-moderate AC voltages, transdermal transport phenomena and enhancement under AC conditions have not been systematically studied and are not well understood. The aim of the present work was to study the fundamental transport mechanisms of square-wave AC iontophoresis using a synthetic membrane system. The model synthetic membrane used was a composite Nuclepore membrane. AC frequencies ranging from 20 to 1000 Hz and AC fields ranging from 0.25 to 0.5 V/membrane were investigated. A charged permeant, tetraethyl ammonium, and a neutral permeant, arabinose, were used. The transport studies showed that flux was enhanced by increasing the AC voltage and decreasing AC frequency. Two theoretical transport models were developed: one is a homogeneous membrane model; the other is a heterogeneous membrane model. Experimental transport data were compared with computer simulations based on these models. Excellent agreement between model predictions and experimental data was observed when the data were compared with the simulations from the heterogeneous membrane model.

Electric Conductivity↗

PubMed2005

Effects of electrophoresis and electroosmosis during alternating current iontophoresis across human epidermal membrane.

Previous studies in our laboratory have demonstrated that skin electrical resistance can be controlled by an alternating current (AC) electric field. By maintaining constant skin resistance, AC iontophoresis has been shown to reduce the iontophoretic flux variability of neutral permeants. Recently, it was found that symmetric square-wave AC could enhance iontophoretic transport of both neutral and ionic permeants by means of electrophoresis and/or electroosmosis in a synthetic membrane system, and a model was presented to describe the experimental results. The objective of the present study was to assess the effects of AC voltage and frequency and direct current (DC) offset on the flux of neutral and ionic model permeants with human epidermal membrane (HEM). Experiments were conducted under two different conditions: constant AC voltage iontophoresis and iontophoresis using constant HEM resistance with DC offset voltage. The following are the main findings in these experiments. In the constant AC voltage study, when the permeability data were compared at the same HEM electrical resistance, it was demonstrated that AC even at high frequency (approximately 1 kHz) could enhance the transport of the ionic permeant (tetraethylammonium ion) across HEM, but no enhancement was observed for the neutral permeant (arabinose). For the ionic permeant flux enhancement, the higher the applied AC voltage, the greater the flux enhancement. There was little or no AC frequency dependence of the flux enhancement in the frequency range of 50-1000 Hz. In the constant HEM resistance study of AC with DC offset, approximately linear relationships were observed between flux enhancement and the DC offset voltage for both the neutral and ionic permeants, and these results were found to be consistent with predictions of the modified Nernst-Planck model for conventional constant voltage DC iontophoresis. When the DC offset voltage was increased, the AC component of the flux enhancement for the ionic permeant decreased, eventually appearing to contribute negligibly to the total flux enhancement at high DC offset voltages.

Electrophoresis↗

PubMed1991

A histopathologic study of retinal lesions inflicted by transscleral iontophoresis.

In the present study, retinal lesions were induced by transscleral iontophoresis (1.5 mA) in rabbits. The size and severity of the lesions increased with the duration of application (2-25 min). No lesion was noted after less than 1 min application. Immediately after 5 min iontophoresis, the edematous retina exhibited necrotic retinal pigment epithelium (RPE), loss of outer segments, and thinning of the inner and outer nuclear layers. At 5 days after iontophoresis, there was a proliferation of RPE cells and macrophages in the subretinal space, with thinning of the inner and outer retinal layers continuing. By day 14, the retina had been reduced to a glial membrane. Immediately after 15 min iontophoresis, the damaged retina appeared in a mummified form containing no cellular elements. By day 5 thereafter, macrophages and actively proliferating RPE cells had been noted in the necrotic retina. By day 14, a glial membrane had formed.

Animals↗

PubMed1994

Effect of pertussis toxin on the response of rat medial prefrontal cortex cells to the iontophoresis of serotonin receptor agonists.

In this study, we examined the response of spontaneously active as well as quiescent cells (L-glutamate-activated) in the rat medial prefrontal cortex (mPFc) to the iontophoresis of 2-methylserotonin (2-Me-5-HT, 5-HT3 receptor agonist), (+/-)-2,5-dimethoxy-(4-iodo-phenyl)-2-aminopropane (DOI, 5-HT2A,2C receptor agonist), 8-hydroxy-N,N-di-propylamino tetralin (8-OH-DPAT, 5-HT1A receptor agonist) and gamma-aminobutyric acid (GABA, a non-selective GABA receptor agonist) after the intracerebral administration of pertussis toxin, an inactivator of the Gi/o protein. This was accomplished using the techniques of extracellular single cell recording and iontophoresis. The administration of pertussis toxin (0.5 microgram, 24 hours before the experiment) into the mPFc did not alter the response of mPFc cells to the iontophoresis of DOI, 2-Me-5HT or GABA compared to saline treated controls. However, the response of mPFc cells to the iontophoresis of 8-OH-DPAT was significantly attenuated in the animals pretreated with pertussis toxin compared to controls. These results suggest that the 5-HT1A but not 5-HT2A,2C or 5-HT3 receptor is coupled to the Gi/o protein.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1995

[Pulsed direct current iontophoresis as a possible new treatment for hyperhidrosis].

Tap water iontophoresis with direct current represents the therapy of choice in palmoplantar hyperhidrosis. Side effects are minor discomfort and skin irritations. Improper use may induce iontophoretic burns at sites of minor skin injuries. The aim of this study was to find ways of minimizing side effects, increasing safety standards and reducing the technical complications of tap water iontophoresis without loss of efficacy. In a blind study, 30 patients with palmar hyperhidrosis were treated with tap water iontophoresis using pulsed direct current of 4.3 kHz or 10.0 kHz. Efficacy and side effects were compared with those of the conventional direct current method as a control. Normal sweat secretion rates of palms were found after an average of ten treatment sessions with the conventional direct current method and after twelve with pulsed direct current of 4.3 or 10 kHz. Treatment with pulsed direct current of 4.3 kHz failed to inhibit palmar hyperhidrosis in two of ten patients. Occasionally, such side effects as discomfort, skin irritation, and mild electric shock occurred when direct current was applied. Using pulsed direct current subjective sensations of discomfort and skin irritation were rare (4.3 kHz) or very rare (10 kHz). Electric shock was completely prevented. Because of the minimal side effects, despite minor loss of efficacy tap water iontophoresis with pulsed direct current can be a valuable alternative treatment for palmar hyperhidrosis.

Adolescent↗

PubMed1975

Cobalt iontophoresis techniques for tracing afferent and efferent connections in the vertebrate CNS.

In recent years several dye and cobalt iontophoresis techniques have been successfully used by invertebrate neurophysiologists for the localization of neuron somata and their processes. The cobalt iontophoresis technique has now been extended for use in the tracing of nerve fiber pathways and the localization of neuron somata in vertebrates. The brain and spinal cord of an animal are removed following perfusion with saline, and placed in a dish of cold saline. A suction electrode, filled with 300 mM cobalt chloride, is then placed over the cut end of the nerve trunk. Cobalt ions are then iontophoresed (by means of a voltage divider) within the nerve fibers, along their course. Following iontophoresis, the brain is bathed in an ammonium sulfide solution to precipitate the cobalt as black cobalt sulfide. The brain is then processed for histological procedures. A wide variety of vertebrates has been used, including amphibians, reptiles, aves and mammals, with uniform success. The cobalt iontophoresis technique presently in use has a wide range of applicability for neuroanatomical studies.

Animals↗

PubMed2005

Reverse iontophoresis of lithium: electrode formulation using a thermoreversible polymer.

This work investigated the use of a thermoreversible gel as a collector vehicle in reverse iontophoresis applications. A 20% (w/w) aqueous gel of Pluronic F127 was a suitable receptor medium to be used at the cathodal chamber. In vitro iontophoresis experiments investigated the simultaneous extraction of lithium (analyte of interest) and sodium (used as an internal standard) into either a control buffer or a gelled receptor. The gelification process at room temperature provided a suitable consistency and contact with the skin surface during the iontophoresis experiments. Subsequent cooling of the gelled solution to 4 degrees C allows an easy recovery of lithium and sodium for later quantification. Both the lithium extraction fluxes and the lithium to sodium ratio of extraction fluxes were linearly related to the subdermal lithium concentration. On the whole, the results show that thermoreversible polymer solutions offer a simple and convenient way to handle samples in reverse iontophoresis studies.

Animals↗

PubMed2004

Non-invasive monitoring of phenytoin by reverse iontophoresis.

Transdermal iontophoresis offers a non-invasive sampling method for therapeutic drug monitoring. This study examined whether iontophoretic extraction (a) is concentration dependent, (b) reflects the subdermal level of unbound drug, (c) follows protein binding changes, and (d) becomes truly non-invasive when a co-extracted compound is used as an internal standard for calibration. Iontophoresis was conducted in vitro using dermatomed pig-ear skin. The subdermal solution was a buffer containing phenytoin at therapeutic concentrations, an internal standard at fixed level, human albumin and/or valproic acid. The ionized form of phenytoin was recovered at the anode by electro-migration, while the neutral form was extracted to the cathode by electroosmosis. A satisfactory correlation between the reverse iontophoretic extracted amount of phenytoin and the subdermal concentration was observed. Iontophoresis extracted only the free fraction of phenytoin. At steady state, reverse iontophoresis monitored changes in free drug concentration provoked in the subdermal compartment. Acetate was introduced at a fixed concentration into the subdermal compartment to act as an 'internal standard'. Subsequently, acetate and the ionized form of phenytoin were co-extracted to the anode. The ratio of the extracted amounts was proportional to the subdermal concentration ratio demonstrating a means by which the method may become truly non-invasive.

Animals↗

PubMed2004

Transdermal iontophoresis of 5-fluorouracil combined with electroporation and laser treatment.

The influence of iontophoresis and other physical enhancement methods such as electroporation and erbium:yttrium-aluminum-garnet (YAG) laser on the skin permeation of 5-fluorouracil (5-FU) was examined. Iontophoresis increased the in vitro transdermal transport of both the anionic and non-ionic forms of 5-FU. A combination of electroporation pretreatment and subsequent iontophoresis resulted in a higher permeation of 5-FU than either technique alone. It appeared that electroporation treatment exerted a disruptive influence on the stratum corneum (SC). The SC layers in the skin were partly ablated by the laser, resulting in a great enhancement effect on the skin permeation of 5-FU. Application of iontophoresis further increased the drug permeation across laser-pretreated skin. The laser was consistently the most potent technique to enhance 5-FU delivery among the physical enhancement methods examined in this study.

Administration, Cutaneous↗

PubMed2005

Effect of lactic acid and iontophoresis on drug permeation across rabbit ear skin.

The aim of this paper was to explore the efficacy of lactic acid as permeation enhancer for drug molecules across the skin. Three model permeants were chosen: acetaminophen (non-ionized), buspirone hydrochloride (cationic drug) and ibuprofen lysine (anionic drug). We also explored the association of lactic acid and iontophoresis as a means of enhancing drug delivery. Permeation experiments were performed in vitro, using rabbit ear skin as barrier. The results obtained indicate that lactic acid has some effects on model drug permeation across the skin. The effect was more evident with the anionic drug ibuprofen. Cathodal intophoresis increased ibuprofen transport, but when lactic acid was associated with cathodal iontophoresis, a concentration-dependent reduction of ibuprofen iontophoretic flux was observed, probably for the competition by the co-ion. The application of electric current (anodal iontophoresis) to a solution of acetaminophen produced an increase in its transport, due to the presence of an electroosmotic contribution; however, the effect of the association of anodal iontophoresis and lactic acid produced no further enhancement.

Acetaminophen↗

PubMed2005

Skin blood flowmotion response to insulin iontophoresis in normal subjects.

In order to explore the mechanisms directly involved in the insulin vasodilatory activity, we studied skin blood flowmotion by means of spectral analysis of the skin forearm laser Doppler (LD) signal registered before and after iontophoresis of insulin in saline (I.S.) (0.1 ml Humulin R 100 IU/ml diluted 1/10 in 0.9% saline) or pure saline (P.S.) (0.1 ml of 0.9% saline) in twenty normal subjects. Skin LD blood perfusion was also measured in conventional perfusion unit (PU; 1 PU=10 mV). Using a Fast Fourier transform algorithm, power density (PD) of the total flowmotion spectrum, from 0.009 to 1.6 Hz, was measured in PU/Hz. Power density of five skin flowmotion frequency intervals (F.I.) within 0.009-0.02 Hz, 0.02-0.06 Hz, 0.06-0.2 Hz, 0.2-0.6 Hz and 0.6-1.6 Hz (referred to endothelial, sympathetic, myogenic, respiratory and heart activity, respectively) was also measured in PU/Hz. The mean skin LD perfusion increment (expressed as percent change from baseline) was significantly higher after I.S. than after P.S. (P<0.001, ANOVA for repeated measures). Skin flowmotion total spectrum mean PD value significantly increased following iontophoresis of both P.S. (from 1.06+/-0.62 to 1.86+/-0.94 PU/Hz, P<0.005) and I.S. (from 1.07+/-0.92 to 2.39+/-1.73 PU/Hz P<0.00005), however, the mean PD increment was significantly higher after I.S. than after P.S. (1.27+/-0.98 PU/Hz versus 0.69+/-0.67 PU/Hz, P<0.05). Only the flowmotion component referred to myogenic activity showed a percent PD increase from baseline significantly higher in response to I.S. than to P.S. iontophoresis (114.5+/-21.8% versus 58.8+/-17.9%, respectively, P<0.05). These findings show that insulin has a vasodilatory activity on skin microvascular district. The higher increase of total blood flowmotion PD and particularly of the component related to the myogenic activity in response to insulin iontophoresis suggests that the cutaneous vasodilatory activity of insulin is, in part, related to an important action of this hormone on skin microvascular smooth muscle.

Adult↗

PubMed2003

Treatment of calcifying tendinitis of the shoulder by acetic acid iontophoresis: a double-blind randomized controlled trial.

OBJECTIVE: To assess the effects of acetic acid iontophoresis on the treatment of calcifying tendinitis of the shoulder. DESIGN: Double-blind randomized controlled trial. SETTING: Ambulatory academic hospital in Quebec, Canada. PARTICIPANTS: Thirty-six subjects with a calcifying tendinitis of the shoulder. INTERVENTIONS: Subjects were randomized into 1 of 2 groups: physiotherapy during 6 weeks (10 sessions) plus acetic acid iontophoresis for the treatment group (n=18) and sham acetic acid iontophoresis for the control group (n=18). MAIN OUTCOME MEASURES: The Shoulder Pain and Disability Index (SPADI), shoulder range of motion (ROM); and radiologic evaluation of shoulder calcifications. RESULTS: Nine patients dropped out, leaving 27 assessable subjects for analysis. Interim analysis showed that, in both groups, treatment led to improvement, as measured by the SPADI score (P=.004), ROM of the shoulder for abduction (P<.001), internal rotation (P=.001), external rotation (P<.001), and the mean number of calcifications per subject (P=.010). Although no formal significant intervention effects (P=.13) were found for the primary endpoint (SPADI), exploratory analyses suggest a greater improvement in the treatment group (P=.001) than in the control group (P=.33). CONCLUSIONS: Despite a trend toward greater improvement in the SPADI score in the treatment group, the use of acetic acid iontophoresis and physiotherapy for the treatment of calcifying tendinitis of the shoulder did not result in better clinical and radiologic effects than those observed in subjects treated by physiotherapyalone.

Acetic Acid↗

PubMedDate not supplied

Induction of gene into the rabbit eye by iontophoresis: preliminary report.

PURPOSE: To assess the transfer of 6-carboxyfluorescein (6-FAM)-labeled phosphorothioate oligonucleotides(S-ODNs) into the ocular tissues, their stability, and possibility of injury to the ocular tissues. METHODS: The S-ODNs(2 mL/eye)were transduced noninvasively into albino rabbit eyes.The iontophoresis group consisted of 6 rabbits (12 eyes); the control group consisted of 2 rabbits (4 eyes) given eye drops containing S-ODNs. Aqueous humor and vitreous humor were collected after iontophoresis, subjected to electrophoresis with a fluorescence DNA sequencer and analyzed by the Gene Scan program. Frozen sections, 10-microm thick, were prepared for observation under a fluorescence microscope. A plasmid 4.7 kbp in size that expresses green fluorescent protein (GFP) was induced into the 18 eyes of 9 rabbits by the same procedure. RESULTS: In the iontophoresis group, S-ODNs were detected in the anterior chamber 5 minutes after electrophoresis began and in the vitreous after 10 minutes. These S-ODNs maintained the same length as at the initial synthesis. The S-ODNs could also be detected in the posterior retina 20 minutes after electrophoresis. No evidence of degeneration or inflammation due to the above procedure was found in the ocular tissues. Fluorescence showing GFP gene expression was found in the cornea, the anterior chamber angle, and the ciliary subepithelial tissues. CONCLUSIONS: These findings show that iontophoresis is an effective method to induce genes into the rabbit eye.

Animals↗

PubMed1978

Practical considerations in iontophoresis of fluoride for desensitizing dentin.

A review of the literature on treatment of dentin hypersensitivity by use of fluorides and fluoride iontophoresis was presented. It was concluded that topical applications of fluoride are modestly effective for treatment of dentin hypersensitivity, but the most rapid and effective relief follows fluoride iontophoresis. This technique has a broad application in dental practice since fluoride iontophoresis was shown to be an effective desenitizer in cavity preparation, before cementation of restorations, and in cases of occlusal wear and enamel hypoplasia. The report also presents a new and effective method for the iontophoresis of fluoride for dentin desensitization.

Dentin Sensitivity↗