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PubMed1987

Transscleral iontophoresis of gentamicin in monkeys.

Experiments in rabbits have shown that the novel technique of transscleral iontophoresis is a safe, effective, noninvasive way to produce high concentrations of antibiotics in the vitreous humor. The authors have now studied the effects of repeated transscleral iontophoresis in the eyes of cynomolgus monkeys. Six treatments with gentamicin sulfate, 1.5 mA for 10 min, were applied to both eyes of three monkeys over a 2-week period. The concentrations of gentamicin in the vitreous humor 24 hr after treatment were determined for each eye on three occasions. The mean concentration was 28 micrograms/ml (range, 11-44 micrograms/ml) after the first treatment and 12 micrograms/ml (range, 2-21 micrograms/ml) after the fifth treatment. Indirect ophthalmoscopy completed after the last treatment showed only small retinal burns up to 2.5 mm in diameter in four eyes in the area of the pars plana over which the electrode had been applied. Electroretinograms were normal after treatment. These experiments confirm the efficacy and safety of transscleral iontophoresis in the primate's eye and suggest that investigations of this potentially useful technique are warranted in humans.

Animals↗
PubMedDate not supplied

[Iontophoresis of forced skin absorption of indomethacin and salicylic acid].

Cutaneous absorption of ionized substances is forced by iontophoresis. This was shown by Pratzel and Hillmeier's investigation of the permeation of salicylic acid (increasing factor 150) and Pratzel and Dittrich's experiments with indomethacin (factor 10) in pigs. In the present paper it is shown that in human volunteers iontophoretic application of indomethacin for one hour onto the skin of the back (surface 1380 cm2) increased indomethacin plasma levels after 2 hours to a maximum of 221 ng/ml, and increased urinary excretion of indomethacin from 24 micrograms (control) to 138.7 micrograms in 5 hours. Iontophoretic application of salicylic acid for one hour daily in human volunteers onto a skin area of 400 cm2 increased serum levels in five days to 690 ng/ml and urinary excretion of salicylic acid and salicyluric acid to 24 mg, as opposed to 2.5 mg by control without current. However, after 30 min iontophoresis only 4 mg is excreted in the urine. In conclusion, if the iontophoresis is practised over a long period of time on large skin areas, systemic effects can be expected.

Administration, Topical↗
PubMed1980

[Intraneoplastic iontophoresis of cytostatics in the overall treatment of esophageal cancer].

The authors report the results of clinical elaboration and testing of the technic of intraesophageal intratumor sarcolysin iontophoresis associated with radiotherapy in 40 inoperable patients with cancer of the thoracic esophagus. A total focal dose of irradiation was on the average 1/3 less compared with the routine one. Iontophoresis was performed by a specially designed electrode with 5-10 mA during 60 minutes. The iontophoresis procedure was followed by irradiation. The immediate good results of the treatment were twice as frequent as in control groups. The treatment proceeded with less pronounced radiation response. An average survival of patients while using chemical drugs intophoresis proved to be equal to control data that is likely to be due to the far-advanced stage of the disease in most patients. An average survival in patients with less tumor proliferation was found to be longer than in analogous control series.

Adult↗
PubMed1994

Evaluation of 2% sodium fluoride iontophoresis as an alternative to lining in Class I cavity preparations--an in vivo study.

The study carried out on 110 permanent teeth in 44 randomly selected patients with age ranging from 8-14 years, to evaluate the efficacy of 2% sodium fluoride iontophoresis as an alternative to cavity lining in Class I preparations. 65 teeth were included in the experimental group (2% sodium fluoride iontophoresis) and 4 teeth in the control group (Zinc phosphate linings). Sensitivity gradings were done on a subjective discomfort scale. From the results, it was found that after cavity preparation, all the teeth (100%) were sensitive to air blast, water jet and probing in varying severity. But after iontophoresis and amalgam restoration the sensitivity reduced to 4.6%. Six months and nine months follow up revealed that all the teeth were vital and asymptomatic.

Adolescent↗
PubMed1983

Double-barreled electrode for simultaneous iontophoresis and single unit recording during movement in awake monkeys.

A double-barreled electrode for simultaneous glutamate iontophoresis and chronic single unit recording from cortical neurons in awake monkeys during voluntary movement is described. Electrode assembly consists of pulling a heated, partitioned capillary tube over a sharpened tungsten rod. Glutamate iontophoresis increased the firing rates of wrist movement related cells an average of 34 Hz during the agonist phase of movement and 27 Hz during the antagonist phase of movement. However, in no case did glutamate iontophoresis alter the detailed structure of the cell's response pattern during wrist movement. This electrode is well suited to chronic recording applications that involve methods such as cross-correlation requiring overlapping activity of neurons and/or muscles. Other applications might involve activation of totally 'silent' neurons to avoid possible sampling bias or to detect effects in post-stimulus time histograms that would otherwise be subliminal.

Animals↗
PubMed2002

Transdermal delivery of indomethacin by iontophoresis.

The objective of this study was to construct a modified equation for the delivery of a drug by iontophoresis. Indomethacin was selected as a model since it has been widely used as a non-steroidal anti-inflammatory drug (NSAID) for external pharmaceutical preparations. The experiments were performed under a constant current in vivo using rat abdominal skin, and the plasma concentration was monitored by HPLC. Pharmacokinetic parameters were obtained from the plasma concentration profiles after intravenous injection. A theoretical value of the transdermal delivery of drug by iontophoresis was calculated from the plasma concentration and pharmacokinetic parameters. The experimental value was evidently higher than the theoretical one, suggesting the enhancement of passive diffusion with an increase of applied current. The modified equation was proposed for the delivery of a drug by iontophoresis incorporating enhanced passive diffusion.

Administration, Cutaneous↗
PubMed1992

[The effect of EBCI Iontophoresis on orthodontic tooth movement in rabbits]

The purpose of this study was to observe the effect of EBC ionophoresis on increasing the rate of tooth movement in rabbits.21 rabbits,in whose lower incisors the standard orthodontic appliances were placed,were divided into 3 groups at rendom which separately received iontoporesis of EBC,iontophosesis and injection of physiological saline at the submucosal area of the lower incisors.The results showed that the animals with EBC iontophoresis obtained tooth movement rate of 4.275+/-0.1214(mm) and the animals with NaCl iontophoresis and injection were respectively 3.337+/-0.4626(mm) and 2.178+/-0.2922(mm).The histological observation had also found the evidence of the ability of EBC to stimulate osteoclasts in preiodontal pression side and osteoblasts in tension.This study suggested that iontophoresis of EBC could play an important role in reconstructing the periodontum and speeding the tooth movement in rabbits.

Journal Article↗
PubMed1984

A fresh look at iontophoresis.

The rate of penetration of fluorescein and gentamicin ions into the anterior chamber of the rabbit was increased more than 100-fold by the passage of 1 mamp; the amount of drug that penetrates is better controlled by iontophoresis than by instillation. The potential value, the safety and the limitations of this procedure are discussed, and a theoretical basis for the increase is provided. Practical methods of using iontophoresis in the clinic are described. A 30-s application should result in a therapeutic level of the antibiotic in the anterior segment over a 12-hour period in eyes with an intact epithelium.

Animals↗
PubMed1975

Anesthesia of the ear by iontophoresis of lidocaine.

Anesthesia of the tympanic membrane and ear canal by the use of iontophoresis of local anesthetics is a painless and safe method of anesthesia for office myringotomy and polyethylene tube insertion, and possibly for surgical use as well. With the use of guinea pig models, the introduction of 4% lidocaine hydrochloride solution in the middle ear space with iontophoresis revealed no toxic effects on the eighth nerve, and epinephrine hydrocloride potentiates the effects of lidocaine and has no protective mechanism on the eighth nerve function.

Action Potentials↗
PubMed1989

Effects of iontophoresis of noradrenaline and stimulation of the periaqueductal gray on single-unit activity in the rat superficial dorsal horn.

Recordings were made with a new form of low-noise carbon fibre microelectrode from 75 units in the superficial laminae of the lumbar dorsal horn of the anaesthetized rat. The response of each unit to adequate stimulation of its peripheral receptive field, to noradrenaline (NA) applied iontophoretically, and to electrical stimulation of the periaqueductal gray (PAG) was investigated. Only units that could be excited by iontophoresis of glutamate (10-100 nA) were analyzed. Recording sites in the spinal cord and stimulation sites in the brainstem were identified histologically at the end of each experiment. Forty-six units with low-threshold receptive fields and small spike amplitudes were found, mainly located in laminae II and III. Both stimulation of the PAG and NA iontophoresis excited the majority (32/46) of these units. The rest were unaffected. Eight high-threshold (HT) units were located in the region of lamina I. Twenty-one wide-dynamic-range (WDR) units were found mainly in deeper laminae. Both WDR and HT units were inhibited by NA and PAG stimulation. This inhibition affected both glutamate-evoked activity and responses to nociceptive stimuli. We suggest that the small LT units are inhibitory interneurones of the substantia gelatinosa (SG), which act on the WDR and HT units to produce nociceptive-specific inhibition. The inhibition can be modality-specific without necessarily being presynaptic because of the laminar arrangement of the dorsal horn. The PAG could thus exert its known antinociceptive effects at least partly via descending noradrenergic axons that excite these SG cells.

Animals↗
PubMed2003

Reverse iontophoresis for noninvasive glucose monitoring: the internal standard concept.

Reverse iontophoresis is used by the GlucoWatch Biographer to noninvasively extract glucose across the skin, allowing a diabetic's glycemia to be evaluated every 10 min over several hours. However, before each use, the device must be calibrated with a blood sample assayed in the conventional way. The objective of this study was to identify an approach by which to avoid this invasive step. The dermal (anodal) side of porcine skin in vitro was bathed in buffered (pH 7.4) solutions containing glucose, at concentrations from 3 to 10 mM, and physiological levels of sodium chloride. Constant current was applied and the cathodal solution contacting the outer skin surface was analyzed periodically for the quantities of Na(+) and glucose extracted by "reverse" electromigration and electroosmosis, respectively. Although the extracted Na(+) flux was invariant, as expected, given the essentially fixed NaCl concentration present in the physiological system, the glucose samples reflected proportionately the subdermal concentration. Equally, the extracted flux ratio (glucose/sodium) varied linearly with the subdermal glucose/sodium concentration ratio; knowing the gradient of this correlation, therefore, means that a measurement of the extraction flux ratio can be used to determine the subdermal glucose concentration (the physiological [Na(+)] being known and fixed). Thus, a refinement of the reverse iontophoresis technology using the simultaneous determination of the extracted fluxes of the analyte of interest (glucose) and of an "internal standard", whose level in the biological system is invariant (Na(+)), may permit a noninvasive sampling methodology free of the need for calibration with a blood sample.

Algorithms↗
PubMed2006

Pharmacokinetics and pharmacodynamics analysis of transdermal iontophoresis of 5-OH-DPAT in rats: in vitro-in vivo correlation.

Pharmacokinetics and dopaminergic effect of dopamine agonist 5-OH-DPAT in vivo were determined following transdermal iontophoresis in rats based on drug concentration in plasma (C(p)) and dopamine levels in striatum (C(DA)). Correlation of the in vitro transport with the pharmacokinetic-pharmacodynamic (PK-PD) profiles was characterized in the transport in dermatomed rat skin (DRS) and rat stratum corneum (RSC). The integrated in vivo PK-PD and in vitro transport models successfully described time course of C(p), C(DA), and in vitro flux in DRS and RSC. Population value of steady-state flux (J(ss)) in vivo (31 nmol/cm(2) . h with 95% confidence interval (CI) = 20-41) is closer to J(ss) in vitro in DRS (61 nmol/cm(2) . h, CI = 54-67) than in vitro J(ss) in RSC (98 nmol/cm(2) . h, CI = 79-117). On the other hand, skin release rate constant (K(R)) in vivo was similar to the K(R) in RSC (4.8/h, CI = 2.4-7.1 vs. 2.6/h, CI = 2.5-2.6). Kinetic lag time (t(L)) in vivo was negligible, which is close to in vitro t(L) in RSC (0.0 h, CI = 0.0-0.1). Based on nonlinear mixed-effect modeling, profiles of C(p) and C(DA) were successfully predicted using in vitro values of J(ss) in DRS with K(R) and t(L) in RSC. A considerable dopaminergic effect was achieved, indicating the feasibility to reach therapeutically effective concentrations of 5-OH-DPAT upon transdermal iontophoresis.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1994

Role of conductivity in iontophoresis. 2. Anodal iontophoretic transport of phenylethylamine and sodium across excised human skin.

The anodal iontophoretic transdermal delivery of a model cation, phenylethylamine (PEA), across excised human skin was investigated to define the role of conductivity in iontophoresis. The ratio of the specific conductance of PEA in deionized-distilled water to that of the solution applied in the donor compartment (buffer+PEA) was employed to assess the relationship between the flux of PEA and the conductivity. The flux of PEA was linearly related to the ratio of specific conductance at 5 and 20 mM PEA for a variety of experimental conditions. A curvilinear relationship was observed at 1 mM PEA concentration, particularly when the conductivity of the donor solution was low. It is therefore hypothesized that a threshold conductivity in solution exists above which a linear relationship between iontophoretic flux and specific conductance is observed. The present study confirms that conductivity of an ion in a solution provides a simple means of estimating the competitive transport between solute and other ions during transdermal iontophoresis.

Buffers↗
PubMed1994

Modulated drug release using iontophoresis through heterogeneous cation-exchange membranes. 2. Influence of cation-exchanger content on membrane resistance and characteristic times.

An implantable drug delivery method using iontophoresis through cation-selective membranes was further developed. Heterogeneous cation-exchange membranes (HCMs) were prepared by mixing conductive sulfonated polystyrene beads into a nonconductive silicone rubber matrix. The membrane resistivity and lag time to steady-state transport of two salts, (+/-)-phenylpropanolamine hydrochloride (PPA) and NaCl, were evaluated during constant current iontophoresis at 37 degrees C as a function of the resin content in the HCMs. A continuous decline in membrane resistivity was observed as fractional resin content (l) was increased over the entire usable region (l = 0.29-0.52), a characteristic that could be described by a percolation scaling law (for an infinite lattice, 3-D geometry). Morphological analysis of the membranes before and after swelling strongly suggested that the conducting clusters of resin beads form during the swelling period prior to use. The response time to steady-state transport of PPA into NaCl during a 40 microA constant current (0.27 cm2) was found to increase with increasing l, but not without decreasing the permselectivity of the HCMs for the drug cation. The lag time effect could be explained in terms of an increasing number of fixed charge groups in the membrane available for transport (mfcA), which was derived from a macroscopic mass balance model. The values of mfcA were also found to be related to the characteristic time of diffusion in a homogeneous transport projection of the HCM (or an effective medium), an essential parameter for future non-steady-state simulations. The characteristic time of diffusion was found to be invariant with changing resin content, suggesting that the membranes are fairly nontortuous (ca. seven beads thick). By assuming that the thickness of the HCM approaches the thickness of its homogeneous projection, an expression was derived to predict lag time to steady-state PPA transport requiring resistance measurements only (provided that the resin capacity is known). There was excellent agreement between the theoretical and experimental lag time to steady-state transport of PPA (r = 0.96, p < 0.001), further implicating the role of membrane resistance in the bi-ionic system. These modeling approaches have already found utility in iontophoretic implant design for prevention of cardiac arrhythmias and may be valuable in future non-steady-state analysis to further develop on-line detection-implant response technology.

Cations↗
PubMed1995

Transdermal iontophoresis and solute penetration across excised human skin.

The potential of transdermal iontophoresis to facilitate drug delivery was evaluated by studying the transport kinetics of model compounds salicylate (anion), phenylethylamine (cation), mannitol (polar neutral compound of low molecular weight), and inulin (polar neutral compound of high molecular weight) using an excised human skin model. The transport kinetics of solutes were determined across both intact and cellophane-tape-stripped dermatomed skin both in the presence and absence of applied current to probe the mechanisms of iontophoretic delivery. Iontophoresis effectively enhanced delivery of all compounds relative to passive transport. The skin is shown to be both ion selective and size selective. On the basis of results from present work and other studies, the "aqueous pathway" of iontophoretic transport is further reinforced.

Administration, Cutaneous↗
PubMed1997

Skin microcirculation during tapwater iontophoresis in humans: cathode stimulates more than anode.

The aim of this controlled study was to evaluate the influence of anode and cathode on skin blood flow by using direct current. Skin microcirculation and skin temperature of 26 healthy subjects (17 men and 9 women, 20-64 years of age) without any vascular diseases were registered when a tapwater iontophoresis was applied. Thermoindifferent water temperature was used to prevent thermic effects on microcirculation. The blood flow measurement was conducted by laser-Doppler flowmetry on the proximal forearm and on the back of the wrist. The skin temperature was measured before and after treatment by an infrared thermometer. In 19 persons there was an intense erythema on the side of the cathode and an only modest one on the side of the anode, while 7 persons showed meager reactions on both sides. The erythema rose strongly from the distal (back of the hand) to the proximal forearm. The comparison of the microcirculation of the arms showed an increase of 120% at the anode and of 700% at the cathode. The differences between the two sides were significant (P < 0.001). After the end of tapwater iontophoresis the skin temperature increased more on the side of the cathode than on the anode side (P < 0.001). The frequency of vasomotion did not change. The vasomotion amplitude increased 67% at the anode (P < 0.05) and 175% at the cathode (P < 0.001). The increased blood flow effect was not age or sex dependent. Although the increased blood flow effect was six times larger on the cathode side, the subjects did not perceive any subjective difference.

Adult↗
PubMed1990

Iontophoresis with an adrenergic alpha-blocker in acoustic overstimulation.

To study the influence of sympathetic innervation on the amount of threshold shift (TS) induced by sound overstimulation, iontophoresis with phentolamine, a known adrenergic alpha-blocker, was performed on awake guinea pigs. The sound exposure following this induced a significantly lesser degree of TS when compared with the control group. These findings indicate that iontophoresis may be of great help in transporting specific ionized chemical compounds through the intact cochlear walls in a completely non-invasive manner for studying cochlear physiology.

Acoustic Stimulation↗