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PubMed2002

A study of lidocaine iontophoresis for pediatric venipuncture.

UNLABELLED: In this randomized, double-blinded, placebo-controlled study, we evaluated the safety and efficacy of lidocaine iontophoresis for the prevention of pain associated with venipuncture in 59 children aged 6-17 yr. Children received either lidocaine HCl 2% with epinephrine 1:100,000 (Active) or the same formulation without lidocaine (Placebo) via a 20 mA/min iontophoretic treatment. Pain during venipuncture was assessed by the subject, parent, and nurse using a 100-mm visual analog scale. Median (interquartile range) visual analog scale scores were significantly lower in the Active versus Placebo groups: subject, 7.0 (2.0-20.8) versus 31.0 (12.0-48.0), P < 0.001; nurse, 5.0 (2.2-10.8) versus 24.0 (9.0-47.0), P < 0.001; and parent, 3.0 (0.8-7.2) versus 20.0 (4.5-43.0), P < 0.002, respectively. Similarly, higher median satisfaction scores were given to the Active versus Placebo group by the three evaluators. Of the 59 subjects completing the study, 10 subjects experienced a total of 12 adverse events that were all graded as mild. In conclusion, lidocaine iontophoresis is safe in children, reduces discomfort associated with venipuncture, and increases satisfaction when compared with the placebo. IMPLICATIONS: In this randomized, double-blinded, placebo-controlled study, we found that dermal anesthesia with lidocaine HCl 2% combined with epinephrine 1:100,000 administered via iontophoresis in children is achieved in 8.8 +/- 2.1 min, reduces discomfort associated with venipuncture, is safe, and increases satisfaction when compared with the placebo.

Adolescent↗

PubMed2004

Enhanced transfollicular delivery of adriamycin with a liposome and iontophoresis.

To find a better way to deliver drugs into hair follicles, we tried two approaches: single topical application using various liposomes; and iontophoresis combined with topical application of ionic liposome. After delivery of adriamycin (ADR) to wax-depilated rat skin, the transport of the drug was examined under fluorescence microscopy. Most liposomal ADR showed more effective transdermal and transfollicular penetration than free ADR. Among tested liposomes, the non-ionic GDL liposome (GDL/CH/POE-10 = glycerol dilaulate/cholesterol/polyoxyethylene-10) was the most selective to hair follicles against skin, while the cationic liposome (GDL/CH/POE-10/DOTAP, dioleoyl trimethylammonium propane) containing monocationic DOTAP was less selective; however, it was better at improving the delivery amount and penetration of ADR into the follicles and skin. The DMPC/DMPG (7/3) formulation of anionic PC liposome (DMPC/DMPG = dimyristoyl-phosphocholine/-phospoglycerol) showed results similar to the cationic liposome. The DMPC/DMPG (3/7) formulation yielded poor results, however, probably because of its increased viscosity and anionic property. Although ADR delivery was enhanced by liposomal formulations, topical applications had some limitations in delivery capacity and speed. To accelerate delivery, iontophoresis was combined with the cationic liposome at positive 0.2-0.4 mA/cm(2) for 20-30 min. The resulting delivery of ADR through follicular routes was excellent. This combination method diffused ADR 3.0-fold more efficiently, rapidly and deeply than single topical application of cationic liposomal ADR. This system also achieved a 3.5-fold higher diffusive follicular delivery than a free ADR/iontophoresis combination. Furthermore, it was demonstrated that the tetracationic lipid DOSPER and hydrophile spermine could serve as a cationic additive instead of the monocationic DOTAP in the liposome. These results suggest that the combinative system of the topically applied cationic liposome followed by iontophoresis has a significant synergistic effect on the transfollicular delivery of ADR.

Administration, Cutaneous↗

PubMed2004

Enhancement of topical 5-aminolaevulinic acid delivery by erbium:YAG laser and microdermabrasion: a comparison with iontophoresis and electroporation.

BACKGROUND: 5-aminolaevulinic acid (ALA) is used as a protoporphyrin IX-precursor for the photodynamic therapy of superficial skin cancer and cutaneous metastases of internal malignancies. However, the permeability of hydrophilic ALA across the skin is very low. OBJECTIVES AND METHODS: The objective of this study was to optimize and enhance the in vitro skin permeation of ALA by two resurfacing techniques: erbium:yttrium-aluminium-garnet (Erb:YAG) laser and microdermabrasion. Light microscopic changes in pig skin caused by these techniques were also compared. The electrically assisted methods, iontophoresis and electroporation, were also used to facilitate ALA permeation across laser- or microdermabrasion-treated skin. RESULTS: Among the modalities tested in this study the Erb:YAG laser showed the greatest enhancement of ALA permeation. The laser fluence was found to play an important role in controlling the drug flux, producing enhancement ratios from 4-fold to 246-fold relative to the control. The skin permeation of ALA across microdermabrasion-treated skin was approximately 5-15-fold higher than that across intact skin. Both the ablated effect of the stratum corneum (SC) and ALA flux were proportional to the treatment duration of microdermabrasion. The application of iontophoresis or electroporation alone also increased the ALA permeation by approximately 15-fold and 2-fold, respectively. The incorporation of iontophoresis or electroporation with the resurfacing techniques caused a profound synergistic effect on ALA permeation. CONCLUSIONS: This basic study has encouraged the further investigation of ALA permeation by laser or microdermabrasion.

Administration, Topical↗

PubMed2004

BOTOX delivery by iontophoresis.

We report two patients with severe palmar hyperhidrosis who responded to BOTOX delivered not by injection, the usual method of delivery, but by iontophoresis. The Botulinum molecule has been considered too large for delivery into the skin this way. However, other large peptides, both non-ionic and cationic, have been delivered successfully by this method, so we suspected that BOTOX could in fact be iontophoresed. Our saline-controlled treatment of these two patients with a small iontophoresis unit (Iomed Phoresor II) allowed small volumes of standard BOTOX dilutions to be used, and demonstrates that iontophoresis can indeed deliver BOTOX successfully. This has important therapeutic potential for the large number of patients with focal hyperhidrosis. They may be spared painful injections, and in more severe cases, invasive surgery.

Adult↗

PubMedDate not supplied

Iontophoresis treatment.

Iontophoresis can be used as a method of treating herpes simplex virus and aphthous gingivostomatis. Idoxuridine has been used for herpes simplex virus, and corticosteroids and antibiotics have been used for aphthous stomatitis. Levamisole hydrochloride has been used for both herpes simplex virus and recurrent aphthous stomatitis. A lidocaine and adrenaline mixture is used with iontophoresis for myringotomy procedures and equalizing tubes. Also, anesthesia of the skin and subcutaneous tissues with lidocaine hydrochloride by iontophoresis are useful for minor surgical procedures ("ouchless surgery").

Gingivitis↗

PubMed2003

Comparison of effects of phonophoresis and iontophoresis of naproxen in the treatment of lateral epicondylitis.

OBJECTIVE: The aim of this study was to compare the effectiveness of naproxen (10%) applied by topical iontophoresis or by phonophoresis in the treatment of lateral epicondylitis. DESIGN: Randomized controlled trial. SETTING: Dokuz Eylül University School of Physical Therapy and Rehabilitation. SUBJECTS: This study was carried out with 61 patients who had lateral epicondylitis. They were randomized into two groups. INTERVENTIONS: Naproxen was applied to the first group using phonophoresis (29 patients--33 extremities) and to the second group using iontophoresis (32 patients--34 extremities). Patients in both groups were treated by other physiotherapy methods (cold pack, progressive strengthening and stretching exercises). OUTCOMES: Pain scores (at rest, during motion, with pressure, weight lifting), grip strength and Nirschl-Petterone Grading System were evaluated before and after treatment. RESULTS: Pain scores decreased, grip strength and Nirsch-Petterone Grading System statistically significantly increased in both groups after treatment (p < 0.05), but there were no statistical differences between groups before or after treatment (p > 0.05). CONCLUSION: The results suggest that iontophoresis and phonophoresis of naproxen are equally effective electrotherapy methods in the treatment of lateral epicondylitis.

Administration, Topical↗

PubMed2000

Recovery of human skin impedance in vivo after iontophoresis: effect of metal ions.

The objective of this study was to investigate the effect of the counter-ion (cation) on the recovery of human skin impedance after iontophoresis in vivo. A series of metal chloride aqueous solutions (NaCl, KCl, CaCl2, and MgCl2) was investigated: first at the same concentration (133 mmol/L) and then at the same ionic strength as a NaCl solution at 133 mmol/L. The influence of hydration alone was also examined as a control. The recovery of human skin impedance was followed in the frequency range 1-1,000 Hz, over a 30-minute period after iontophoresis during which 3 impedance spectra were recorded. The results revealed that at t = 30 minutes post-iontophoresis, skin impedance was approximately 3 times greater than the value immediately after the cessation of current passage. However, the results showed that the nature of the cation had no effect on recovery, regardless of whether the ions were at the same concentration or at an equivalent ionic strength. A simple parallel RC-equivalent circuit model for skin was used to determine the resistive (R) and capacitive (C) contributions to skin impedance. An analysis of variance on the calculated R and C values did not show any differences between the electrolytes used at the 2 different ionic strengths.

Adult↗

PubMed2000

A combination of iontophoresis and the chelating agent 1,10 phenanthroline act synergistically as penetration enhancers.

The peroxovanadium compound VO(O2)2 1,10 phenanthroline (bpV(phen)) is capable of lowering blood glucose levels. It is not available in oral form, but it is effective when delivered transdermally. Iontophoresis can significantly reduce the lag time of this response in vivo when compared with passive penetration. To better mimic in vivo insulin release, we explored the effects of various iontophoretic current durations on dermal penetration of bpV(phen). Iontophoretic transport was not related to total applied charge, as steady-state flux was equivalent for current durations ranging from 15 minutes to 9 hours. We hypothesized that the unexpectedly large transport after just 15 minutes of current was caused by an increase in passive penetration of bpV(phen) induced by iontophoresis. Iontophoretic pretreatment with the chelating agent 1,10 phenanthroline increased passive penetration of bpV(phen), whereas neither the nonchelating isomer 1,7 phenanthroline nor the less potent chelator EDTA were effective. The use of 1,10 phenanthroline as a penetration enhancer for other chemicals was examined with the amino acids alanine and leucine. Fifteen minutes of 1,10 phenanthroline iontophoresis enhances alanine transport 11.4-fold over passive, whereas the 1,7 phenanthroline increased transport by a factor of 4.6 and the iontophoretic control of ethanol by 1.9. Surprisingly, phenanthroline did not enhance 3H leucine penetration. The reasons for this selectivity are not clear and warrant further investigation. Overall, the data suggest that chelating agents, specifically 1,10 phenanthroline, may be used as penetration enhancers for the delivery of certain compounds.

Alanine↗

PubMed2003

Transdermal iontophoresis of insulin. Part 1: A study on the issues associated with the use of platinum electrodes on rat skin.

We have studied the issues associated with the use of platinum electrodes for transdermal iontophoretic delivery of peptides, using insulin as a model peptide. Insulin permeation was studied using full-thickness rat skin by varying the donor solution pH as a function of electrode polarity. The stability of insulin under the iontophoretic conditions was studied using TLC, SDS-polyacrylamide gel electrophoresis and HPLC. Large pH shifts were observed during anodal iontophoresis (AI), when the donor solution pH was above the isoelectric point of insulin and in cathodal iontophoresis (CI), when the donor solution pH was below the isoelectric point of insulin. The direction and magnitude of electroosmotic flow was influenced by pH of the donor solution and the electrode polarity. On the other hand, the buffer used to maintain the pH governed the contribution of electrorepulsion to the overall transport of insulin. Electrochemical degradation of insulin was significant during AI at pH 7.4. Among the pH investigated, AI of insulin at pH 3.6 and CI at pH 8.35 were better, as the pH shift was relatively less and electrochemically more stable during iontophoresis as compared with other pH. In summary, the pH shift caused by platinum electrodes had a significant influence on the permeation and stability of insulin.

Animals↗

PubMed2000

Iontophoretic transdermal delivery of ketoprofen: effect of iontophoresis on drug transfer from skin to cutaneous blood.

The objectives of this study were to develop a method for kinetic analysis of drug transfer to cutaneous blood flow and to evaluate the effect of iontophoresis on drug transfer to cutaneous blood. Cathodal iontophoresis of ketoprofen (non-steroidal anti-inflammatory drug) was conducted to rats (applied electrical current 0.14 and 0.70 mA/cm2; application time 5, 15, 30, 60 and 90 min), and the drug concentrations in skin, cutaneous vein and systemic vein were determined. Transfer rate of ketoprofen from skin to cutaneous blood (R(SC)) was calculated by modifying a physiological pharmacokinetic model. The time-course of R(SC) for 0.70 mA/cm2 showed that the value of R(SC) was initially increased, following a gradual decrease with time after 30-min application. The effect of electrical current on drug transfer to cutaneous blood flow was estimated from the comparison to passive diffusion (without electrical current). The R(SC) value at 30-min application was almost proportional to the electrical current, and the enhancement ratio for 0.14 and 0.70 mA/cm2 was 17 and 73, respectively. Consequently, our results suggest that the change of drug transfer to cutaneous blood flow by iontophoresis may depend on the application period and the magnitude of electrical current.

Administration, Cutaneous↗

PubMed2001

[Enhancing effect of switching iontophoresis on transdermal absorption of glibenclamide].

Glibenclamide(GLI) is widely used as an oral hypoglycemic drug in the treatment of non-insulin dependent diabetes mellitus (NIDDM). We investigated The enhancing effect of switching iontophoresis on the transdermal absorption and reduction of skin irritation to develop a transdermal dosage form of GLI. The 0.1% of Gli suspensions in 0.2 M tris-HCl buffer of pH 7.4, 8.0 and 8.5 were prepared as donor solutions. We examined drug permeation through the excised rat abdominal skin, drug absorption in rats and reduction of skin irritation after application of switching iontophoresis for 1 h using DC 10 V. The solubility of GLI in 0.2 M tris-HCl buffer increased with a rise in pH. In the permeation study, GLI was permeated continuously and the cumulative amount of permeated GLI increased using an alkaline donor solution. In the drug absorption study, the application group of pH 8.5 gave higher plasma concentration levels than those of pH 7.4 and 8.0 groups. The skin irritation evoked by the application of iontophoresis was pathologically studied. A total irritation score (TIS) was estimated as a judging standard for the skin damage. The TIS value increased dependently with a rise in pH. However, it was considered that the skin irritations were not serious and small matters. The results demonstrate the possibility of iontophoretic transdermal administration of GLI and the effect of drug solubility in the donor solution on the absorption of GLI.

Animals↗

PubMed2005

Iontophoresis as a means of delivering antibiotics into allograft bone.

Allograft bone is widely used in orthopaedic surgery, but peri-operative infection of the graft remains a common and disastrous complication. The efficacy of systemic prophylactic antibiotics is unproven, and since the graft is avascular it is likely that levels of antibiotic in the graft are low. Using an electrical potential to accelerate diffusion of antibiotics into allograft bone, high levels were achieved in specimens of both sheep and human allograft. In human bone these ranged from 187.1 mg/kg in endosteal (sd 15.7) to 124.6 (sd 46.2) in periosteal bone for gentamicin and 31.9 (sd 8.9) in endosteal and 2.9 (sd 1.1) in periosteal bone for flucloxacillin. The antibiotics remained active against bacteria in vitro after iontophoresis and continued to elute from the allograft for up to two weeks. Structural allograft can be supplemented directly with antibiotics using iontophoresis. The technique is simple and inexpensive and offers a potential means of reducing the rate of peri-operative infection in allograft surgery. Iontophoresis into allograft bone may also be applicable to other therapeutic compounds.

Animals↗

PubMed1999

Transdermal iontophoresis. Part I: Basic principles and considerations.

The skin has increasingly become a route for the delivery of drugs with a range of compounds being considered for transdermal delivery generating a great deal of interest in this area of research. The passive delivery of most compounds across the skin is limited due to the barrier properties afforded by stratum corneum, the outermost layer of the skin. Transdermal iontophoresis is an effective technique for physically facilitating the transport of permeants across the skin by using electromotive force. It is being extensively explored as a potential means for delivery of hydrophilic, large and charged molecules and is also believed to be a future method of choice for peptides and proteins. In this context, this review focuses mainly on the basic principles and considerations of transdermal iontophoresis with particular emphasis on modeling, devices and parameters influencing transdermal iontophoresis.

Administration, Cutaneous↗

PubMed2006

Exogenous zinc improves blood fluidity but has no effect on the mechanisms of vascular response to acetylcholine iontophoresis in humans.

Recent findings in cellular signaling function of zinc through the mobilization intracellular calcium or by inducing ATP release suggest that extracellular zinc plays an important role in many physiological functions. However, such an extracellular signaling action of zinc for most cells is not known. Therefore, we investigated whether zinc plays any role in endothelium- dependent acetylcholine (ACh)-induced vasodilatation in microvascular beds. Transdermal iontophoresis was used to transport ACh through the forearm skin and cutaneous perfusion was measured using a laser Doppler flowmeter (LDF). Experiments were repeated using (1) zinc instead of ACh to test the effect of zinc ions alone and (2) concomitant iontophoresis of ACh and zinc to explore the effect of zinc on ACh-induced vasodilatation. Although zinc augments blood flow, curve-fitting to LDF signals indicate that zinc has no effect on the neural and endothelial component of ACh-induced vasodilatation. Additionally, no effect of Zn2+ on blood flow was found during its iontophoresis alone. Therefore, it is suggested from the Fourier analysis of LDF signals that the Zn+ might influence blood fluidity by its action on red blood cells deformability/ aggregability during a high-blood-flow condition, which might, in turn, decrease blood viscosity and improve blood flow in vivo.

Acetylcholine↗

PubMed2006

Transdermal iontophoresis.

Iontophoresis is a technique used to enhance the transdermal delivery of compounds through the skin via the application of a small electric current. By the process of electromigration and electro-osmosis, iontophoresis increases the permeation of charged and neutral compounds, and offers the option for programmed drug delivery. Interest in this field of research has led to the successful delivery of both low (lidocaine) and high molecular drugs, such as peptides (e.g., luteinising hormone releasing hormone, nafarelin and insulin). Combinations of iontophoresis with chemical enhancers, electroporation and sonophoresis have been tested in order to further increase transdermal drug permeation and decrease possible side effects. In addition, rapid progress in the fields of microelectronics, nanotechnology and miniaturisation of devices is leading the way to more sophisticated iontophoretic devices, allowing improved designs with better control of drug delivery. Recent successful designing of the fentanyl E-TRANS iontophoretic system have provided encouraging results. This review will discuss basic concepts, principles and applications of this delivery technique.

Administration, Cutaneous↗

PubMedDate not supplied

Short-term effects of iontophoresis on the structure of the guinea pig tympanic membrane.

Guinea pig tympanic membrane was anesthetized iontophoretically. The animals were sacrificed between 2 h and 4 days after the anesthesia and the tympanic membrane was studied histologically by light microscopy and transmission electron microscopy. Edema in the subepidermal connective tissue layer and detachment of the basement membrane from the basal cell layer were observed 2 h after iontophoresis. Eight and 12 h later, the epidermal layer between the handle of the malleus and the bony annulus peeled and retracted towards the bony annulus, leaving only hornified outer epidermis on the fibrous layer. Four days after iontophoresis, the retracted margin of the epidermal layer became greatly thickened and evidence of hyperplasia and migration was observed. This study has demonstrated that iontophoresis of the tympanic membrane produces remarkable histological changes. However, no perforation was observed.

Anesthesia, Local↗

PubMed2005

[Protective effect of low-level laser irradiation on acupuncture points combined with iontophoresis against focal cerebral ischemia-reperfusion injury in rats].

OBJECTIVE: To investigate the effects of low-level laser irradiation on acupuncture points combined with iontophoresis against brain damage after middle cerebral artery occlusion (MCAO) in rats. METHODS: Sixty-nine SD rats were randomly divided into five groups, including normal group, sham operation group, model group, electro-acupuncture group and low-level laser irradiation on acupuncture points combined with iontophoresis group (LLLI group). The cerebral ischemia-reperfusion (I/R) model was established by thread embolism of middle cerebral artery. The rats in the LLLI group, as well as the electro-acupuncture group were given treatment as soon as the occlusion finished (0 hour) and 12, 24 hours after the occlusion. We observed the changes of neurological deficit scores and the body weight of the rats at different time. The activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in the ratos brain tissue were tested. RESULTS: The neurological deficit score of the LLLI group was significantly lower than that of the model group. The body weight and the activity of SOD of the rats decreased slightly, and the content of MDA decreased significantly after the treatment. CONCLUSION: The low-level laser irradiation on acupuncture points combined with iontophoresis can prevent focal cerebral ischemia-reperfusion injury. One of its mechanisms may be increasing the activity of SOD and decreasing the damage of the oxidation products to the body.

Acupuncture Points↗

PubMed1995

The effects of glutamate iontophoresis on single cell responses and inter-neuronal interactions in the kitten visual cortex.

We studied the effect of glutamate (Glu) micro-iontophoresis on visual responses (PSTHs) and cross-correlograms of neurones recorded simultaneously in the cortex of 4-6 weeks old kittens. PSTHs and cross-correlograms were tested before, during and after Glu injections and compared with adult cats data from previous experiment. Before the injection cross-correlogram shapes and numbers did not differ in young and adult cats, whereas PSTHs differed dramatically. Glu iontophoresis typically elevated background PSTHs levels rather than peak responses in young kittens. In adult animals the opposite effect predominated. After the termination of iontophoresis visual responses were enhanced in 21% of kitten neurones. In adult cats this effect was not observed. In kittens, a clear increase of cross-correlogram strength was recorded in one neuronal pair (3.6%) after the injection terminated. In adult cats similar effect was also found in 3% of pairs.

Animals↗