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At least 19 recordsLinked to original sources
PubMed2002

Improvement on conventional constant current DC iontophoresis: a study using constant conductance AC iontophoresis.

The purpose of the present study was to compare conventional constant direct current (DC) transdermal iontophoresis with a new constant conductance alternating current (AC) iontophoresis method. The new method was developed with the intent of reducing flux drift during iontophoresis and minimizing skin-to-skin variability. The constant conductance AC iontophoresis studies involved three electrical components: (1) an initial applied potential used to decrease the human epidermal membrane (HEM) electrical resistance to a target level of either 1.5 or 3.0 k Omega cm(2), (2) an applied 50 Hz square-wave AC with a variable potential adjusted to maintain the HEM conductance at the target level during the transport study, and (3) a low voltage DC offset of 0 (passive), 0.25, or 0.40 V applied simultaneously with the AC to assist permeant transport. Current densities of 0.13 and 0.26 mA/cm(2) were chosen for the conventional constant current DC iontophoresis studies. Mannitol was used as the probe permeant for all studies. The constant current DC studies showed significant increases in mannitol flux with time during a given experiment and large skin-to-skin variability. Compared to the constant current DC experiments, the mannitol flux remained more constant during the constant conductance AC iontophoresis and skin-to-skin variability was significantly reduced. On a mechanistic level, changes in the transport properties during constant current DC iontophoresis indicate changes in the membrane parameters such as porosity, effective pore size, and/or pore surface charge density during the conventional method of iontophoresis. The results from the constant conductance AC iontophoresis transport studies imply that this method effectively maintains the membrane parameters that affect transport at a constant state this providing for a relatively constant permanent flux.

Biological Transport↗
PubMed2003

In vitro and in vivo comparisons of constant resistance AC iontophoresis and DC iontophoresis.

A previous in vitro constant electrical resistance alternating current (AC) iontophoresis study with human epidermal membrane (HEM) and a model neutral permeant has shown less inter- and intra-sample variability in iontophoretic transport relative to conventional constant direct current (DC) iontophoresis. The objectives of the present study were to address the following questions. (1) Can the skin electrical resistance be maintained at a constant level by AC in humans in vivo? (2) Are the in vitro data with HEM representative of those in vivo? (3) Does constant skin resistance AC iontophoresis have less inter- and intra-sample variability than conventional constant current DC iontophoresis in vivo? (4) What are the electrical and the barrier properties of skin during iontophoresis in vivo? In the present study, in vitro HEM experiments were carried out with the constant resistance AC and the conventional constant current DC methods using mannitol and glucose as the neutral model permeants. In vivo human experiments were performed using glucose as the permeant with a constant skin resistance AC only protocol and two conventional constant current DC methods (continuous constant current DC and constant current DC with its polarity alternated every 10 min with a 3:7 on:off duty cycle). Constant current DC iontophoresis was conducted with commercial constant current DC devices, and constant resistance AC iontophoresis was carried out by reducing and maintaining the skin resistance at a constant target value with AC supplied from a function generator. This study shows that (1) skin electrical resistance can be maintained at a constant level during AC iontophoresis in vivo; (2) HEM in vitro and human skin in vivo demonstrate similar electrical and barrier properties, and these properties are consistent with our previous findings; (3) there is general qualitative and semi-quantitative agreement between the HEM data in vitro and human skin data in vivo; and (4) constant skin resistance AC iontophoresis generally provides less inter- and intra-subject variability than conventional constant current DC.

Diffusion Chambers, Culture↗
PubMed2004

Correlation of transdermal iontophoretic phenylalanine and mannitol transport: test of the internal standard concept under DC iontophoresis and constant resistance AC iontophoresis conditions.

The purpose of this study was to test the feasibility of using an internal standard approach to predict the transdermal flux of phenylalanine (Phe) across human epidermal membrane (HEM) in vitro during iontophoresis of constant direct current (DC), constant skin resistance alternating current (AC) with DC offset (AC-plus-DC), symmetric constant resistance AC (AC-only), and constant current DC with the application of a polyelectrolyte. Under the constant current DC and AC-plus-DC conditions, a linear relationship between the permeation of Phe and that of mannitol was observed with a slope close to unity. The ratios of the Phe permeability coefficients to those of mannitol during iontophoresis with different HEM samples were essentially constant with significantly smaller inter-sample and intra-sample variabilities than those of the raw Phe permeability coefficient data. This demonstrates that mannitol is a good internal standard for predicting the transdermal iontophoretic flux of Phe under these two conditions. On the other hand, the correlations of the permeability coefficients of Phe and mannitol under the AC-only iontophoresis and iontophoresis with the polyelectrolyte are poorer than those observed during DC and AC-plus-DC iontophoresis. The poor correlations are believed to be related to Phe being a zwitterion and its anionic form in HEM. Previously, iontophoretic transport of glucose has been demonstrated to be essentially the same as that of mannitol. The good correlations between Phe and mannitol transport across HEM during DC and AC-plus-DC iontophoresis in the present study therefore suggest that glucose and its extraction can be used as the internal standard for iontophoretic Phe monitoring.

Administration, Cutaneous↗
PubMed1994

Iontophoresis of a model peptide across human skin in vitro: effects of iontophoresis protocol, pH, and ionic strength on peptide flux and skin impedance.

This study deals with effects of electrical (current density, frequency and duty cycle) and chemical (buffer pH and ionic strength) conditions on the flux of the octapeptide, 9-desglycinamide, 8-arginine-vasopressin (DGAVP), through dermatomed human skin. A pulsed constant current was applied during iontophoresis. The anode faced the anatomical surface of the skin samples inside the diffusion cells. The resistive and capacitative components of the equivalent electrical circuit of human skin could be calculated by fitting the voltage response to a bi-exponential equation. The skin resistance prior to iontophoresis varied between 20 and 60 k omega.cm2. During iontophoresis a decrease of skin resistance and an increase of the series capacitances was observed, which were most pronounced during the first hour of iontophoresis; thereafter both quantities gradually levelled off to an apparent steady state value. The reduction of the resistance during iontophoresis increased non-linearly with increasing current density between 0.013-0.64 mA.cm-2. The steady state resistance and capacitances did not vary significantly with frequency and duty cycle of the current pulse. There was no pH dependence of skin resistance at steady state. Between pH 4 and 10, the steady state peptide flux had a bell-shaped pH-dependence with a maximum of 0.17 nmol.cm-2.h-1 at pH 7.4, which is close to the I.E.P. of the peptide. Lowering the ionic strength from 0.15 to 0.015 M NaCl increased the steady state flux at pH 5 and pH 8 by a factor 5 to 0.28 +/- 0.21 and 0.48 +/- 0.37 nmol.cm-2.h-1, respectively. Together these observations suggested that DGAVP is transported predominantly by volume flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Arginine Vasopressin↗
PubMed1992

Iontophoresis generates an antimicrobial effect that remains after iontophoresis ceases.

Iontophoresis required chlorine-containing compounds in the medium for effective microbial population reduction and killing. After iontophoresis ceased, the antimicrobial effect generated by iontophoresis remained but slowly decreased. Antimicrobial effects of iontophoresis may be related to the generation of short-lived chlorine-containing compounds.

Candida albicans↗
PubMed1999

Pore induction in human epidermal membrane during low to moderate voltage iontophoresis: A study using AC iontophoresis.

The present study aimed to investigate new pore induction as a flux-enhancing mechanism in human epidermal membrane (HEM) with low to moderate voltage electric fields. The extent of pore induction and the effective pore sizes of these induced pores were to be assessed using a low frequency (12.5 Hz) low to moderate voltage (2. 0 to 4.0 V) square-wave alternating current (ac) "passive" permeation method (ac iontophoresis). This ac approach was to allow for inducing and sustaining a state of pore induction in HEM while permitting no significant transport enhancement via electroosmosis; thus, transport enhancement entirely due to new pore induction (enhanced passive permeation) was to be assessed without any contributions from electroosmosis. Good proportionality between the increase in HEM permeability and its electrical conductance was found with the "passive" transport data obtained during square-wave ac iontophoresis using urea as the model permeant. Typically, at 3.0 to 4.0 V, HEM conductance increases (and permeability increases) ranged from around 3- to 30-fold. These results appear to be the first direct evidence that new pore induction in HEM is a significant flux enhancing mechanism under moderate voltage conditions. The extents of pore induction in HEM under low frequency moderate voltage (2.0 to 3.0 V) ac, pulsed direct current (dc), and continuous dc were also compared. The extents of pore induction from square-wave ac and pulsed dc were generally of the same order of magnitude but somewhat less than that observed during continuous dc iontophoresis at the same applied voltage and duration, suggesting less extent of pore induction with reversing polarity or when a brief delay is provided between pulses to allow for membrane depolarization. The average effective pore sizes calculated for the induced pores from the experimental data with urea and mannitol as probe permeants and the hindered transport theory were 12 +/- 2 A, which are of the same order of magnitude as those of preexisting pores determined from conventional passive diffusion experiments.

Algorithms↗
PubMed1993

Iontophoresis with alternating current and direct current offset (AC/DC iontophoresis): a new approach for the treatment of hyperhidrosis.

Tap-water iontophoresis (TWI) using direct current (DC) is the most effective therapy in palmoplantar hyperhidrosis. Side-effects of this method are discomfort, with burning and tingling, and skin irritation, including erythema and vesicles. Incorrect use may induce iontophoretic burns at sites of minor skin injury. Elaborate safety measures are required to prevent electric shock. The aim of this study was to minimize side-effects and to increase technical and safety standards of TWI, without loss of efficacy. In a controlled blind study, treatment of palmar hyperhidrosis by alternating current (AC) or by AC with DC-offset (AC/DC) was compared with the conventional DC method. Palmar hyperhidrosis was completely controlled after an average of 11 treatments by either AC/DC iontophoresis or the conventional DC method. Virtually no effect was seen when AC without DC-offset was used for TWI. There were no signs of cutaneous irritation, or subjective sensations of discomfort when AC with or without DC-offset was employed. AC/DC iontophoresis should become the treatment of choice for palmoplantar hyperhidrosis. The mechanism of action is unknown. It is hypothesized that an interrupted stimulus-secretion-coupling leads to a functional disturbance of sweat secretion.

Adolescent↗
PubMed1990

Transport mechanisms in iontophoresis. I. A theoretical model for the effect of electroosmotic flow on flux enhancement in transdermal iontophoresis.

Bulk fluid flow or volume flow in the direction of counterion flow is a probable mechanism for enhanced flux of uncharged species by iontophoresis. Both the electrical volume force effect, resulting from the interaction of the "ion atmosphere" and the electric field, and an induced osmotic pressure effect produce volume flow in the same direction as counterion flow through the membrane. Since each of these effects is proportional to the membrane charge and the imposed electric field, we classify both as electroosmotic flow. This research develops a detailed theoretical model which allows the effect of volume flow on flux enhancement to be evaluated. A detailed theoretical result for the electroosmotic flow coefficient also results from the analysis. The model assumes that transport occurs in three types of aqueous pores: positively charged, neutral, and negatively charged. For hairless mouse skin (HMS), pore size, charge, and number are evaluated from transference number, volume flow, and electrical resistance data. The flux enhancement ratio is J1/J1D = sigma Ai alpha i/[1-exp(-alpha i)], where i = pore type, and the summation runs over the three pore types. Ai is the area fraction of pore type i effective for transport; J1 and J1D are flux of species 1 with and without the electric field, respectively; and alpha i is given by alpha i = F(-delta phi/RT)[zeta 1 + (-zeta mi)Bari2Cmi(Gi + F)].(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗
PubMed1995

Iontophoresis for enhancing penetration of dermatologic and antiviral drugs.

Iontophoresis is the process of introducing ionic drugs into the body for therapeutic purposes. Although iontophoresis has the potential for systemic therapy, it has mainly been used for local therapy at body surfaces. Many ionic drugs are available including lidocaine, epinephrine, methylprednisolone succinate, dexamethasone phosphate, several antivirals, various antibiotics, and other specific drugs. The use of an indicated ionic drug by iontophoresis offers a broad potential for promoting the development of more effective therapies in dermatology. Iontophoresis of ionized drugs provided a 20-60 fold increase in penetration over topical application. Iontophoresis for dermatological use requires that: a) a charged drug be placed at an electrode having a polarity the same charge as the drug, b) the condition or disease under treatment be at or near the body surface, and c) a modern, sophisticated source of direct current, with appropriate accessories, be used. The current source must have features that make it not only effective, but also safe for application to the patient. Modern systems for application of drugs by iontophoresis have features that make the process simple and efficient for use in practice. Iontophoresis has a long history of use, having been suggested for various therapies for many years in medicine, physical therapy and dentistry. Pilocarpine iontophoresis is a preferred method for cystic fibrosis detection. Also, lidocaine iontophoresis has been advocated to anesthetize the tympanic membrane before myringotomy. Anesthesia of the skin to a depth of 1.0 cm or more has been reported in double-blind studies of human volunteers. Local anesthesia by iontophoresis was reported to be effective for: 1) cutaneous cutdowns in patients requiring kidney dialysis, 2) delicate eyelid surgery, as the sole anesthetic, 3) preinjection topical anesthesia, and 4) shave biopsies of skin lesions. The use of iontophoresis for treating difficult cases of hyperhydrosis is quite popular among dermatologists. The present report emphasizes uses of iontophoresis in dermatology and is divided into discussion of studies using iontophoresis for postherpetic neuralgia, local anesthesia, antiviral therapy, and for corticosteroid therapy of nonspecific inflammatory lesions. Over 1250 patients have been treated for postherpetic neuralgia by corticosteroid iontophoresis at 6 medical centers with 60-80% of patients showing a major therapeutic response with return to a tolerable pain level. Double-blind studies of varicella zoster (active and postherpetic) and herpes simplex have proven that iontophoresis is a valuable modality for treating viral diseases of the skin. Many other uses for iontophoresis have been proposed in the literature that involve several hundred research papers, several textbooks and many book chapters. Review of the literature supports the concept that iontophoresis provides an optimal method for drug application in therapy of surface tissues.

Antiviral Agents↗
PubMed2006

Enhanced oligonucleotide delivery to mouse retinal cells using iontophoresis.

PURPOSE: To study the combination of oligodeoxynucleotides (ODNs) intravitreous injection and saline transpalpebral iontophoresis on the delivery of ODNs to photoreceptors in the newborn rd1/rd1 mice. METHODS: Cathodal or anodal transpalpebral iontophoresis (1.43 mA/cm(2) for 5 min) was applied to eyes of postnatal day 7 (PN7) rd1/rd1 mice immediately before the intravitreous injection of ODNs. The effect of cathodal iontophoresis after ODNs injection was also evaluated. The influence of current intensity (0.5, 1.5, and 2.5 mA) was assayed with cathodal iontophoresis performed prior to ODNs injection. The duration of current-induced facilitation of ODNs delivery to photoreceptors was evaluated for 6 h following iontophoresis. One group of control eyes received cathodal iontophoresis prior to the intravitreous injection of phosphate buffered saline (PBS) or hexachlorofluorescein (Hex). The second control group received ODN or Hex intravitreous injection without iontophoresis. The penetration of fluorescent ODNs in the outer nuclear layer (ONL) was quantified by image analysis of the ONL fluorescence intensity on cryosection microphotographs. Integrity of ODN was assessed using acrylamide gel migration after its extraction from the retina of treated mice. The integrity of retinal structure, 1 and 24 h after iontophoresis, was analyzed using light and electron microscopy. RESULTS: Transpalpebral anodal or cathodal saline iontophoresis enhanced the penetration of ODNs in all retinal layers. Cathodal iontophoresis was more efficient than anodal iontophoresis in enhancing the tissue penetration of the injected ODN. Photoreceptor delivery of ODN was significantly higher when cathodal saline transpalpebral iontophoresis was applied prior than after the injection. The extent of enhanced tissue penetration decreased in parallel to the increased interval between iontophoresis application and the intravitreous injection. Current of 1.5 mA was safe and optimal for the delivery of ODNs to the ONL. One hour after iontophoresis followed by injection, ODN extracted from the retina of treated eyes remained intact. Histology and electron microscopy observations demonstrated that iontophoresis using the optimal parameters did not induce any permanent tissue alterations or structure damage. CONCLUSIONS: Saline transpalpebral iontophoresis facilitates the penetration of injected ODNs in photoreceptors for at least 3 h. This method may be considered for photoreceptor targeted gene therapy.

Animals↗
PubMed2004

Magnetic resonance imaging study of current and ion delivery into the eye during transscleral and transcorneal iontophoresis.

PURPOSE: The objectives were to determine by nuclear magnetic resonance imaging (MRI) the target sites of ion delivery in the eye during iontophoresis, compare transscleral and transcorneal ocular iontophoresis, and monitor the distribution of a probe ion in the anterior chamber and vitreous after iontophoretic delivery. METHODS: Thirty-minute 2-mA anodal constant current transscleral and transcorneal iontophoresis (current density, 10 mA/cm(2)) was performed on three New Zealand White rabbits in vivo. Intravitreal injection and passive delivery were the controls. Transscleral and transcorneal iontophoresis experiments were conducted with the electrode device placed in the superior cul-de-sac away from the limbus and on the cornea adjacent to the limbus, respectively. During iontophoresis, the current delivered into the eye was monitored using a probe ion (Mn(2+)) with MRI. The distributions of the ion in the aqueous and vitreous humor after iontophoresis, passive delivery, and intravitreal injection were also determined by MRI. RESULTS: With the short application time, passive diffusion did not deliver a significant amount of the ion into the eye. Whereas transscleral iontophoresis delivered the ion into the vitreous, transcorneal iontophoresis delivered the ion into the anterior chamber. The current pathways during iontophoresis were mainly from the electrode into the eye, perpendicular to the electrode-eye interface beneath the electrode. Electric current along the surface of the globe was relatively minimal. With the present transscleral iontophoresis protocol, the ion penetrated the sclera and traveled as far as 1.5 mm from the electrode-conjunctiva interface into the vitreous. For transcorneal iontophoresis, the ion penetrated the cornea and filled the entire anterior chamber. CONCLUSIONS: MRI can be a useful technique in the study of the penetration of probe compounds in the eye during and after iontophoresis, such as in iontophoresis protocol and device testing. Ocular pharmacokinetic studies using MRI are noninvasive and provide real-time data without perturbation and compound redistribution that can occur during dissection and assay in traditional pharmacokinetic studies. With MRI, it was shown that transscleral iontophoresis, transcorneal iontophoresis, and intravitreal injection deliver ions to different parts of the eye.

Animals↗
PubMed1997

Localized delivery of heparin to angioplasty sites with iontophoresis.

Drug delivery by iontophoresis involves the application of an electric field to move selectively charged drug molecules across biological membranes. The purpose of this study was to assess the efficacy of intravascular iontophoresis in the local delivery of heparin to balloon angioplasty sites by using a recently designed iontophoretic catheter. In vivo heparin iontophoresis was assessed in 33 rats and 21 pigs in four protocols designed to measure the technical determinants of intramural drug deposition, the pharmacokinetics and localization of coronary delivery, and the effect of this technique on platelet deposition following balloon injury. First, iontophoresis of 3H-heparin into the aorta of 33 rats was performed to determine the effects of iontophoretic current, iontophoretic membrane balloon initiation pressure, iontophoresis time, and heparin concentration on intramural drug deposition. Second, iontophoresis of 3H-heparin was performed in 16 porcine coronary arteries to quantitate immediate drug delivery and subsequent wash-out over 24 h. Third, iontophoresis of fluorescent heparin was performed in 8 porcine coronary arteries to define intramural localization of locally delivered drug. Fourth, 111In-labeled platelet deposition was measured 1 h following balloon angioplasty and local iontophoretic heparin delivery in 16 porcine carotid and iliac vessels. Contralateral control vessels that were dilated with the same size balloon and treated with iontophoresis of saline served as controls. Rat aortic studies demonstrated that iontophoresis resulted in 13 times more intramural heparin deposition than passive delivery (passive: 0.3 +/- 0.4 microgram, iontophoresis: 4.6 +/- 1.6 micrograms, P < 0.0004). Iontophoretic membrane balloon inflation pressure had no significant effect on intramural drug deposition, but longer iontophoresis times and higher heparin concentrations resulted in higher levels of intramural heparin (P < 0.05). Porcine coronary studies demonstrated successful intramural deposition of heparin in all arteries without adverse electrical or hemodynamic sequelae, with persistence of the drug for at least 24 h. Localization studies demonstrated immediate deposition of fluorescent heparin in the intima and internal elastic lamina, with subsequent rapid diffusion of the drug into the media. Porcine platelet studies demonstrated that heparin iontophoresis decreased platelet deposition following balloon injury by approximately 66% compared with saline-treated control vessels (heparin-treated: 1.46 +/- 2.51 x 10(8), control: 4.27 +/- 7.02 x 10(8), P = 0.001). This study has demonstrated that local intramural heparin delivery is feasible with an intravascular iontophoretic catheter. Following intracoronary heparin iontophoresis in the porcine model, intramural drug is detected for at least 24 h. Local delivery of heparin with this technique significantly decreases early platelet deposition following balloon injury in peripheral porcine arteries.

Angioplasty, Balloon↗
PubMed2005

Evaluation of constant current alternating current iontophoresis for transdermal drug delivery.

Previous studies in our laboratory have demonstrated that alternating current (AC) iontophoresis can significantly decrease skin electric resistance and enhance the transport of charged permeants across skin. Flux variability of neutral permeants during AC iontophoresis was also found to be less than that of conventional direct current (DC) iontophoresis. The objectives of the present study were to evaluate flux enhancement of constant current AC transdermal iontophoresis and compare the AC flux with that of constant current DC iontophoresis. Iontophoresis studies of AC amplitude of 1, 2, and 5 mA were conducted in side-by-side diffusion cells with donor solution of 0.015, 0.15, and 1.0 M tetraethylammonium (TEA) chloride and receiver solution of phosphate buffered saline (PBS) using human epidermal membrane (HEM). Conventional constant current DC iontophoresis of 0.2 mA was also performed under similar conditions. TEA and mannitol were the model permeants. The following are the major findings in the present study. The flux of TEA increased proportionally with the AC current for all three TEA chloride concentrations and at the AC frequency used in the present study. When the permeant and its counter ion were the only ionic species in the donor chamber, the fluxes during DC iontophoresis were weakly dependent of its donor concentration. The fluxes of TEA during constant current AC iontophoresis were moderately related to the donor concentration with the highest TEA flux observed under the 1.0 M TEA chloride condition although the relationship between flux and donor concentration was not linear. A trend of decreasing electroosmotic transport with increasing donor TEA chloride concentration was observed with significant sample-to-sample variability during DC iontophoresis. Mannitol permeability was also observed to decrease with increasing TEA chloride concentration in the donor under the AC conditions, but data variability under AC was significantly smaller than that under DC. The results in the present study indicate that constant current AC iontophoresis under conditions tolerable to human (2 and 5 mA) can provide predictable fluxes that were lower than but of comparable magnitude as those of conventional constant current DC iontophoresis (0.2 mA).

Administration, Cutaneous↗
PubMed1996

Efficacy of iontophoresis in the rat cornea.

BACKGROUND: Iontophoresis can enhance penetration of drugs into tissues. We examined the extent of penetration of gentamicin into the cornea of rats during iontophoresis and the effect of varying the concentrations of gentamicin, the duration of iontophoresis and the current densities during iontophoresis. METHODS: Eight groups of rats underwent corneal iontophoresis using gentamicin dissolved in agar. Low and high concentrations of gentamicin were used, as well as low and high current densities and long and short durations of iontophoresis. Control groups received topical or subconjunctival gentamicin, topical saline solution and mock iontophoresis with the agar-gentamicin mixture. The Mann-Whitney test was used for statistical evaluation. RESULTS: Highly bactericidal concentrations of gentamicin were obtained in all the iontophoresis-treated corneas. The high concentration compared to the low concentration of gentamicin in agar significantly increased the concentration of gentamicin in the corneas, as did the longer duration of iontophoresis. However, higher current intensity did not significantly enhance the drug concentration in the cornea. CONCLUSION: Iontophoresis with a concentrated gentamicin-agar mixture may provide a rapid increase of gentamicin levels in the cornea.

Absorption↗