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PubMed1990

Transport mechanisms in iontophoresis. II. Electroosmotic flow and transference number measurements for hairless mouse skin.

Previous studies suggest that bulk fluid flow by electroosmosis is a significant factor in iontophoresis and may provide an explanation for the observed enhanced transport of neutral species. In a charged membrane, the solution carries a net charge and thus experiences a volume force in an electric field, which causes volume flow (Jv) in the direction of counterion flow. Jv data were obtained for hairless mouse skin (HMS) as a function of pH, concentration of NaCl, current density, and time. Volume flow was measured by timing fluid movement in horizontal capillary tubes attached to the anode and cathode (Ag/AgCl) compartments. By convention, the sign of Jv is taken as positive when the volume flow is in the same direction as positive current flow. Experimental mean values were in the range 0 to +37 microliters/cm2 hr, depending on the experimental conditions. Volume flow of this magnitude is large enough to have significant impact on flow of both ions and neutral species. The positive sign for Jv indicates that HMS is negative in the pH range studied (3.8-8.3). Jv decrease with time, decrease with increasing NaCl concentration, are much lower at pH 3.8 than at the higher pH's, and increase with current density. Effective transference numbers, determined from membrane potential measurements, showed significant pH dependence, consistent with a small negative charge on the membrane at mid pH's and charge reversal around pH 4. Both electrical resistance and Jv data indicate changes in transport properties occur when HMS is subjected to an electric field.

Animals↗

PubMed1988

A new system for in vitro studies of iontophoresis.

This report describes a new iontophoretic diffusion cell that allows both electrodes to be applied to the same side of the same piece of skin. The cell permits a better approximation of the in vivo situation than do conventional side-by-side cells. The unique construction of the cell allows nonliquid material to be applied to the skin surface and makes it possible to investigate horizontal transport paths. Preliminary results utilizing the cell are described. Iontophoretic enhancement of morphine and clonidine delivery across full-thickness hairless mouse skin has been achieved. The importance of pH control in these experiments is apparent. Further experiments with morphine indicate that, for this drug at least, iontophoretically driven lateral transport within the skin is unimportant. Because the cell design allows significant parallels to the use of iontophoresis in vivo, we suggest that it will prove to be a useful tool in the determination of fundamental structure/transport relationships under the influence of an externally applied current.

Animals↗

PubMed1994

Characterization of convective solvent flow during iontophoresis.

During iontophoresis under neutral pH conditions, there is a net convective flow of volume (electroosmosis) from anode to cathode leading to the enhanced transport of dissolved polar (but uncharged) solutes in the same direction. The objective of this study was to address the following unresolved questions with respect to electroosmotic transport: [1] Whether the efficiency of electroosmotic transport is solute size-dependent and, if so, how severe is this dependence? [2] Is electroosmosis linearly related to current density in the same way that the iontophoretic flux of charged species appears to be? [3] Are positively charged permeants able to influence their own electrotransport across the skin (by modifying the net charge on the membrane and altering, as a result, the permselectivity) and, if so, why and to what extent? Electroosmosis was assessed from the iontophoreically driven fluxes of mannitol, sucrose and lactose across hairless mouse skin in vitro. It was found that:- (a) The electroosmotic transport rate of mannitol is similar to that of the disaccharides, sucrose and lactose, when examined under identical conditions. The dependence of electroosmotic flux upon molecular size requires study of solutes having a wider range of MW than those considered here. (b) Electroosmotic flow from anode-to-cathode increases with applied current density; similarly, convective flow in the opposite direction diminishes with increasing current density. Apparently, there is correlation between the net movement of solvent and the total flux of ions across the skin. (c) The permselectivity of skin can be 'neutralized' by driving, iontophoretically, a cationic, lipophilic peptide (specifically the leutinizing hormone releasing hormone (LHRH) analog, Nafarelin) into the membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2003

Effects of fatty acids and iontophoresis on the delivery of midodrine hydrochloride and the structure of human skin.

PURPOSE: The purpose of this work was to investigate if fatty acids can increase the iontophoretic delivery of midodrine hydrochloride through human dermatomed skin and to observe the effects of iontophoresis and fatty acids on skin using SEM. METHODS: After prehydration for 1 h, human dermatomed skin was treated with 0-0.3 M fatty acids (oleic acid, linoleic acid, decanoic acid, and lauric acid) in propylene glycol (PG) for 1 h. Then the fatty acid solution was replaced by 1% midodrine hydrochloride aqueous solution, and 0.1 mA/cm2 constant current was applied. Samples were taken over 24 h and analyzed by HPLC. After the treatments outlined above, the epidermis was separated, fixed with glutaraldehyde, and dehydrated for SEM. RESULTS: SEM studies revealed that only 1 h of treatment with fatty acids opened up the tightly compact stratum corneum cell layer, and the permeation study showed a significant increase of the permeability of skin to midodrine hydrochloride after fatty acid treatment. CONCLUSIONS: Using 5% oleic acid pretreatment, with the electrical current offset at 0.1 mA/cm2, the daily delivery of midodrine hydrochloride can provide an adequate clinical application. The enhancement of passive and iontophoretic delivery by fatty acids may be occurring through the same mechanism.

Adjuvants, Pharmaceutic↗

PubMed2003

Transdermal delivery of timolol and atenolol using electroporation and iontophoresis in combination: a mechanistic approach.

PURPOSE: The purpose of this work was to study the effect of electroporation on iontophoretic transport of two beta-blockers, timolol (lipophilic) and atenolol (hydrophilic), and to have a better understanding of the mechanism of combination. METHODS: The transdermal delivery of these beta-blockers through human stratum corneum was studied in three-compartment diffusion cells. The transport of mannitol was evaluated to assess the electroosmotic flow. RESULTS: The iontophoretic transport of timolol was decreased by electroporation because the high accumulation of the lipophilic cation timolol in the stratum corneum resulted in a decrease of electroosmosis. In contrast, electroosmosis was not affected by atenolol, and the iontophoretic transport of atenolol was increased by electroporation. CONCLUSIONS: Using two different beta-blockers, we showed that lipophilicity and positive charges affect the electrotransport of drugs. Understanding the effect of the physicochemical properties of the drug, as well as the electrical parameters, is thus essential for the optimization of transdermal drug delivery by a combination of electroporation and iontophoresis.

Administration, Cutaneous↗

PubMed2000

Review of intraurethral suppositories and iontophoresis therapy for erectile dysfunction.

This brief review examines the history of the intraurethral (IU) pharmacotherapy for the treatment of erectile dysfunction (ED). Emphasis is placed on the design, study endpoints and results of a limited number of clinical trials undertaken with PGE(1)-MUSE to demonstrate the efficacy of this unique delivery system. Next, the theory of the iontophoretic technique of drug delivery is discussed. Clinical data collected while applying these methods are presented, but are thus far limited to treatment of patients with Peyronie's disease. Iontophoresis as a drug delivery alternative may gain popularity with ED patients who fail other types of therapy or in patients with other penile disorders. International Journal of Impotence Research (2000) 12, Suppl 4, S86-S90.

Alprostadil↗

PubMedDate not supplied

Topical delivery of lidocaine in healthy volunteers by electroporation, electroincorporation, or iontophoresis: an evaluation of skin anesthesia.

BACKGROUND AND OBJECTIVES: This study was designed to compare the onset, duration, and depth of local anesthesia after the topical delivery of lidocaine using electroporation (EP), electroincorporation (EI), and iontophoresis (IP) in healthy volunteers. EP and EI were performed with prototype devices and IP with a commercial drug/device product. METHODS: A double-blind, crossover study design was used for 10 randomized volunteers selected for EP treatment with either 4%, 10%, or 20% lidocaine or placebo normal saline. Because it was impossible to blind between IP, EP, and EI, an open label study with randomized volunteers was selected for IP and EP treatments. Onset and duration of anesthesia was determined by measuring warm sensation, cool sensation, and hot pain; depth of anesthesia was determined by measurement of pain sensation to a 27-gauge needle passed through the skin. RESULTS: For EP, all concentrations of lidocaine produced significant changes from baseline on 2 or 3 efficacy measures, however, the 4% concentration appeared to be the most efficacious when delivered by the EP method. The EP and EI methods produced a significant elevation in all 3 thermal thresholds, whereas IP produced significant elevations in cool and warm thresholds only. However, IP resulted in a greater depth of anesthesia. Plasma lidocaine levels were undetectable. CONCLUSIONS: The transdermal delivery of lidocaine by IP, EP, and EI results in similar surface skin anesthesia; however, IP results in a greater depth of anesthesia. Reg Anesth Pain Med 2001;26:229-238.

Administration, Topical↗

PubMed2002

In vivo transscleral iontophoresis of amikacin to rabbit eyes.

The objectives of these studies were to determine the amount and distribution of the aminoglycoside antibiotic amikacin delivered to rabbit eyes following transscleral iontophoresis and to determine the inter-study reproducibility of delivery over three identical studies. New Zealand White rabbits (N = 6 per dose group) were treated with a 200-mg/mL amikacin solution at 0, 2, 3 or 4 mA of (+) DC current for 20 minutes. Amikacin concentrations in eye tissues were highest with the 4-mA treatment. Concentrations for all three studies at this current were approximately 5.4, 40, 41, 343, and 92 mcg/g in the vitreous humor, anterior segment, non-treated hemisphere of the sclera, treated hemisphere of the sclera, and retina/choroid, respectively. These values were approximately 27, 50, 40, 10, and 13 fold greater than in the 0-mA control group and are well above the in vitro minimum inhibitory concentrations (MICs) for this drug. Inter-study reproducibility (measured as %CV) depended on the tissue type and treatment group and ranged from 8% for the retina/choroid to 51% for the anterior segment in the 4-mA group. Pretreatment with topical proparacaine hydrochloride local anesthetic did not affect amikacin delivery and total drug delivered was not affected by delivery time for the same total charge administered. Therapeutically relevant amounts of amikacin were delivered into eye tissues in a reproducible and controllable manner.

Amikacin↗

PubMed1995

Influence of age and gender on skin vessel reactivity to endothelium-dependent and endothelium-independent vasodilators tested with iontophoresis and a laser Doppler perfusion imager.

BACKGROUND: The aim of this study was to evaluate the influence of age and gender on skin vessel reactivity to one endothelium-dependent vasodilator (acetylcholine, ACh), and two endothelium-independent vasodilators with different modes of action (nitroprusside and isoprenaline). METHODS: The substances were iontophoresed into the skin and the results were mapped through a newly developed laser Doppler perfusion imager. Thirty-four healthy, nonsmoking individuals without any medication and without atopic constitution participated in the study. The subjects, 13 men and 21 women, 18 to 80 years of age, were divided into subgroups according to age and gender. RESULTS: A correlation to age for the vascular responses to nitroprusside and, to a lesser extent, ACh was shown for the women (p = .0036 and .0920 respectively). Differences were also observed between the age and gender subgroups with respect to their response to these two substances: young and, to a lesser extent, middle-aged women differed from elderly women and middle-aged and elderly men. The response to isoprenaline was affected neither by age nor gender. CONCLUSIONS: The results of the study suggest that skin vessel reactivity to nitroprusside and, to a lesser extent, ACh is age dependent. This might reflect both functional and structural changes in skin vasculature with aging. Gender differences for these two substances are also suggested, with women exhibiting a greater increase in perfusion after iontophoresis than men. However, higher vasoconstrictor tone among the women may have influenced the results.

Acetylcholine↗

PubMed1986

Iontophoresis of vidarabine monophosphate for herpes orolabialis.

The cutaneous application of antiviral agents was studied by iontophoresis, a process that increases penetration of most drugs 20- to 60-fold. Twenty-seven subjects with vesicular orolabial herpes were treated one time in a double-blind, placebo-controlled clinical study: nine received vidarabine monophosphate (ara-AMP), nine received acyclovir (ACV), and nine received NaCl. Ara-AMP-treated lesions yielded lower titers of virus after 24 hr compared with lesions treated with NaCl or ACV (P less than .05). Ara-AMP significantly decreased the duration of shedding of virus (P less than .05) and time to dry crust (P less than .05) compared with the other two agents. There was a trend toward decreased healing time after ara-AMP treatment.

Acyclovir↗

PubMed1997

Topical administration of prostaglandin E1 with iontophoresis for skin flap viability.

This study was performed to investigate the capability of iontophoretic delivery of prostaglandin E1 (PGE1) and the effect of this treatment on the viability of skin flaps on the rat dorsum model as described by Hammond and Ronald in 1993. The PGE1 level in the tissue sample under the electrode was assessed with radioimmunoassay. The iontophoretic treatment (for 20 minutes at 4 mA) with PGE1 solution (20 micrograms PGE1 in 2 ml saline) showed a significant increase of PGE1 in the flap tissue under the negative electrode (p < 0.05). Very little increase was observed after the iontophoresis of saline alone. This was not statistically significant. Iontophoretic treatment was given for 5 consecutive days following flap elevation. The survival area on the seventh postoperative day was significantly greater in the PGE1-treated flaps than that of either the control or saline-treated flaps. These results confirm the beneficial effect of iontophoretic treatment with PGE1 on the augmentation of skin flap viability.

Administration, Topical↗

PubMed1991

Focal blockade of single unit synaptic transmission by iontophoresis of antagonists.

We have assessed the use of iontophoresis for investigating the pharmacology of synaptic transmission from individual presynaptic neurones in-vivo, by modifying extracellular focal synaptic potentials (FSPs) recorded by spike-triggered averaging. FSPs from two types of excitatory neurone (muscle spindle primary afferents and expiratory bulbospinal neurones) and from one inhibitory interneurone were studied in the thoracic ventral horn of anaesthetized cats. The antagonist of excitatory amino acids at non-NMDA receptors, DNQX, blocked the FSPs from the first two, as did bicuculline for the third. Thus the FSPs were generated by excitatory amino acids acting via non-NMDA receptors and GABA, respectively. The postsynaptic neurones were probably motoneurones. Merits and limitations of the method are discussed.

Animals↗

PubMed1991

Intracellular free calcium in isolated vestibular hair cells and potassium iontophoresis.

The resting free calcium level was measured in 128 isolated mammalian vestibular sensory cells using the calcium-sensitive dye fura-2. Iontophoresis was used to apply short, localised and limited pulses of K+ which evoked dynamic changes in intracellular free calcium concentration. While most of the type I hair cells tested showed brief reversible and specific calcium responses, some were unresponsive. The changes in intracellular free calcium were also measured by videomicroscopic analysis. Iontophoretic application of K+ ions is shown to be a suitable method for inducing fast, transient changes in intracellular free calcium in vestibular hair cells. This technique could be useful for applying several ions and charged molecules such as amino acids in in-vitro cellular methods.

Animals↗

PubMed1990

Properties of transdermal histamine iontophoresis: differential effects of season, gender, and body region.

Histamine iontophoresis is demonstrated to be a reliable model for the study of inflammatory skin responses. It has the advantage of a non-invasive and uniform mode of application and is free of unwanted side effects. The wheal and flare responses to histamine are linearly related to dose over a wide range of stimulus strengths (r = 0.88). In summer, wheal responses were smaller, probably due to increased thickness of the epidermis. Female subjects generally expressed larger wheal responses than males, presumably due to differences in epidermal thickness and structure. There were significant regional differences in wheal, flare, and laser Doppler recorded flux responses. Ratings of itch sensations also showed clear, but less pronounced, differences of body regions. Significant regional differences of wheal and flare responses existed. Sensory discrimination of different stimulus levels was demonstrated with visual analogue scale ratings.

Administration, Cutaneous↗

PubMed2005

Double-blind, crossover comparison of olopatadine and cetirizine versus placebo: suppressive effects on skin response to histamine iontophoresis.

Olopathadine, a newly developed histamine H1-receptor antagonist, was compared with cetirizine in its suppressive effects on histamine-induced wheal and flare reaction using an iontophoresis technique in a double-blind, crossover, placebo-controlled fashion. As a result, olopathadine was found to have effects comparable to cetirizine. This finding may predict the efficacy of this new H1-antagonist in treating pruritic skin diseases.

Administration, Oral↗

PubMed1977

Tap water iontophoresis in palmo-plantar hyperhidrosis.

Plain tap water iontophoresis as a method of treatment of idiopathic palmo-plantar hyperhidrosis was evaluated. In the present study, different strengths of current were used for varying periods of time and the treatment was given 6 days a week, until the patients became euhidrotic. Whereas previous workers have used the two electrodes in separate pans, we, in one study, placed them in the same pan of tap water, so that electrolysis occurred at the electrodes on which palms or soles were resting, the current passing through the medium. It was observed that, irrespective of the method used, euhidrosis of palms or soles were achieved. The time and the amount of current required to produce euhidrosis were significantly greater with the single pan technique (average 14-1 sittings in Group I) as compared to the separate pan method (average 7-09 sittings in group II) (t = 3-41, P less than 0.01). The euhidrosis persisted for between 6 and 8 months (average 6-26 months). In our study 90% of the patients treated developed anhidrosis on both the anode and cathode treated palms or soles. In 10% of the subjects, the effect was, however, greater on the anodal side.

Adolescent↗

PubMed1986

A new device for the treatment of hyperhidrosis by iontophoresis.

A new device for the treatment of hyperhidrosis by iontophoresis is described. Twenty-five patients have so far been treated, six with hyperhidrosis of the palms, 13 with hyperhidrosis of the soles and six with axillary hyperhidrosis. In 21 cases there was an excellent result. The effect of the treatment usually lasted for several weeks. Maintenance treatment every 4-6 weeks was found to be required.

Adult↗

PubMed1989

The effect of iontophoresis of lignocaine in the treatment of tinnitus.

Lignocaine is the only drug available that suppresses tinnitus when given intravenously, but the mechanism and the site of its action are not well understood. Iontophoresis, a method by which chemical agents may be transported by electrical current from the ear canal throughout the tympanic membrane into the middle ear, could be expected to have a suppressive effect on tinnitus because the drug is brought so close to the cochlea. In the present study none of the 46 patients reported the suppression of tinnitus to a non-annoying level. Neither lignocaine nor any of its metabolites was found in blood sampled during the period of this treatment.

Adult↗