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PubMed1998

Mechanism of transport enhancement of LHRH through porcine epidermis by terpenes and iontophoresis: permeability and lipid extraction studies.

PURPOSE: The purpose of this study was to investigate the effect of 5% terpenes (i.e., limonene, carvone, thymol, and cineole)/ethanol (EtOH) and iontophoresis on the in vitro permeability of luteinizing hormone releasing hormone (LHRH) through the porcine epidermis and biophysical changes in the stratum comeum (SC) lipids by fourier transform infrared (FT-IR) spectroscopy. Methods. The porcine epidermis was pretreated with enhancer for 2 h. The permeability measurement system included Franz diffusion cells, Ag/AgCl electrodes, and SCEPTOR iontophoretic power source. FT-IR spectroscopy was performed to assess the possible contribution of lipid extraction to the transport enhancement of LHRH. RESULTS: Terpenes in combination with EtOH significantly (p < 0.05) increased the flux of LHRH in comparison with the control (epidermis which was not enhancer treated). Iontophoresis further enhanced (p < 0.05) the flux of LHRH through terpenes/EtOH treated epidermis in comparison with their passive permeability. Reversibility studies showed that the post-recovery passive flux of LHRH through 5% limonene in EtOH/iontophoresis treated epidermis was significantly (p < 0.05) decreased but did not significantly recover to the baseline flux (i.e., flux through control epidermis). The SC treated with terpenes/ EtOH showed a decrease in peak heights and areas for both asymmetric and symmetric C-H stretching absorbances in comparison to untreated SC. A greater percent decrease in peak heights and areas was obtained by limonene/EtOH. However, treatment of the SC with terpenes/EtOH followed by iontophoresis did not further decrease the percentage of peak height and area over and above terpene/EtOH suggesting that iontophoresis alone does not cause SC lipid extraction. CONCLUSIONS: Terpenes/EtOH increased LHRH permeability by enhancing the extraction of the SC lipids. Iontophoresis synergistically enhanced the permeability of LHRH through terpenes/EtOH treated epidermis. Thus, terpenes can be used as chemical enhancers in combination with iontophoresis to enhance the transdermal delivery of peptides such as LHRH.

Administration, Cutaneous↗

PubMed1998

Localization of a FITC-labeled phosphorothioate oligodeoxynucleotide in the skin after topical delivery by iontophoresis and electroporation.

PURPOSE: The aim of this study was to verify the hypothesis that the application of high voltage to the skin enhances both stratum corneum and keratinocyte permeability. Therefore, the transport of FITC labelled phosphorothioate oligonucleotides (FITC-PS) administered by passive diffusion, iontophoresis or electroporation was localized. METHODS: Fluorescent microscopy and laser scanning confocal microscopy were used to visualize the FITC-PS transport at the tissue and cell level respectively in hairless rat skin after electroporation (5 x (200 V approximately 500 ms) or iontophoresis (same amount of charges transferred). RESULTS: FITC-PS did not penetrate the viable skin by passive diffusion. Molecular transport in the skin upon electroporation or iontophoresis was localized and implied mainly hair follicles for iontophoresis. In the stratum corneum, the pathways for FITC-PS transport were more transcellular during electroporation and paracellular during iontophoresis. FITC-PS were detected in the nucleus of the keratinocytes a few minutes after pulsing. In contrast, iontophoresis did not lead to an uptake of the oligomer. CONCLUSIONS: The internalization of FITC-PS in the keratinocytes after electroporation confirms the hypothesis and suggests that electroporation, which allows both efficient topical delivery and rapid cellular uptake of the oligonucleotides, might be useful for antisense therapy of epidermal diseases.

Administration, Topical↗

PubMed2003

Lidocaine iontophoresis for local anesthesia before shave biopsy.

BACKGROUND: Lidocaine iontophoresis is a method of topical anesthesia in which lidocaine is driven into the skin under the influence of electric current. OBJECTIVE: To compare lidocaine iontophoresis to placebo for topical anesthesia before shave biopsy in adult patients. METHODS: This was a single-center, double-blind, placebo-controlled evaluation of iontophoresis of 2% lidocaine with 1:100,000 epinephrine in patients undergoing shave biopsy. Patients were evaluated for sensation to pinprick after iontophoresis. After completion of the procedure, those patients who did not receive supplemental lidocaine rated the pain associated with the procedure using a 10-cm visual analog scale. The investigator also evaluated the patient's pain after biopsy. Treatment sites were examined for evidence of adverse events such as erythema, urticaria, or burns. RESULTS: Forty-one patients undergoing shave biopsy for evaluation of skin lesions were enrolled. Nineteen of 21 patients in the lidocaine group versus 2 of 20 placebo patients required no supplemental anesthesia (P<0.001). The pain reported by the patient on the visual analog scale subsequent to the procedure was significantly lower in the lidocaine group (P<0.001). In concordance with the results reported by the patients, investigators rated pain lower in the lidocaine group (P<0.001). Blanching and/or erythema occurring at the iontophoresis-treated site in 37 of 41 patients resolved within 1 hour. There were no other treatment-related events. CONCLUSIONS: Lidocaine iontophoresis is a safe and effective method of administering topical anesthesia before shave biopsy in adult patients.

Administration, Topical↗

PubMed1988

Transscleral and transcorneal iontophoresis of vancomycin in rabbit eyes.

We examined the ability of transscleral and transcorneal iontophoresis to deliver vancomycin into the aqueous humor, the vitreous humor, and the cornea of rabbit eyes. Control eyes receiving subconjunctival injection (25 mg) attained peak aqueous, vitreous, and corneal concentrations (mean +/- S.E.M.) of 14.73 +/- 0.35 mcg/ml (at 4 hours after injection), 1.10 +/- 0.78 mcg/ml (2 hours), and 1167 +/- 63 mcg/g (1 hour), respectively. Eyes receiving transscleral iontophoresis (3.5 mA for 10 minutes) attained significantly higher vitreal levels than controls: 6.33 +/- 0.25 mcg/ml (p less than 0.001; 1 hour), 13.43 +/- 2.32 mcg/ml (p less than 0.01; 2 hours), 11.93 +/- 0.76 mcg/ml (p less than 0.001; 4 hours), 8.40 +/- 0.60 mcg/ml (p less than 0.001; 8 hours). Eyes receiving transcorneal iontophoresis (0.5 mA for 5 minutes) attained earlier and significantly higher aqueous and corneal levels than controls. Aqueous humor levels were 16.20 +/- 3.19 mcg/ml (p less than 0.05; 1 hour) and 20.20 +/- 0.43 mcg/ml (p less than 0.001; 2 hours). Corneal levels were 10799 +/- 755 mcg/g (p less than 0.001; 0.5 hour), 4856 +/- 606 mcg/g (p less than 0.005; 1.0 hour), 2185 +/- 71 mcg/g (p less than 0.001; 2 hours), and 710 +/- 112 mcg/g (p less than 0.025; 4 hours). Corneal endothelial cell counts were decreased by 8.8% (p = 0.08) after transcorneal iontophoresis of vancomycin and 5.4% (p less than 0.02) following Balanced Salt Solution (BSS). However, corneal thickness were not significantly increased by iontophoresis of either vancomycin or BSS. These experiments show that transscleral and transcorneal iontophoresis are efficacious in delivering high concentrations of vancomycin into the aqueous and vitreous humor and the cornea.

Animals↗

PubMed2003

Effectiveness of iontophoresis with alternating current (AC) in the treatment of patients with palmoplantar hyperhidrosis.

Conventionally, iontophoresis employing direct current (DC) has been used in the treatment of palmoplantar hyperhidrosis, but this is accompanied by side effects such as pain and burns. In the present study, a prototype apparatus using alternating current (AC) was constructed, and iontophoresis with AC was performed in palmoplantar hyperhidrosis patients to determine its effectiveness. The average amount of perspiration of the palmoplantar hyperhidrosis patients was significantly reduced after the third session when iontophoresis treatments were performed once per week. By the eighth treatment, perspiration was reduced to nearly the normal level, and there were no particular side-effects during the treatment period. This treatment therefore appears to be both safe and effective. The treatment effect tended to appear sooner when alternating current iontophoresis was combined with the administration of anticholinergic drugs than when alternating current iontophoresis was used alone. Alternating current iontophoresis is an effective treatment for palmoplantar hyperhidrosis. Guidelines for this treatment for patients with palmoplantar hyperhidrosis will need to be established in the future.

Adult↗

PubMed1995

New treatment of atrophic acne scars by iontophoresis with estriol and tretinoin.

BACKGROUND: Common treatment of atrophic acne scars consists of invasive methods such as dermabrasion, chemopeeling, or implantation of bovine collagen. In our study a new noninvasive treatment method consisting of local iontophoresis is demonstrated. Local iontophoresis was performed with either estriol--a mainly topically active estrogen--or with tretinoin. PATIENTS AND METHODS: Eighteen women were treated with estriol iontophoresis twice weekly for a period of 3 months. In addition to photographic and clinical documentation of the skin, venous blood for determination of serum levels of prolactin and estradiol according to standard radioimmunoassay methods was obtained monthly. Tretinoin iontophoresis was performed according to the same time schedule in 28 patients (19 women and 9 men) with atrophic acne scars. RESULTS: Improvement of acne scars was observed in 93% of patients treated with tretinoin iontophoresis and in 100% of the group treated with estriol iontophoresis. No hormonal changes were noted in the estrogen group. Side effects involving the skin appeared in the tretinoin group in 4 cases and consisted of increased dryness and of retinoid dermatitis. CONCLUSION: Both treatments were shown to be clinically effective in decreasing acne scars and persistence of effects. This promising new therapeutic approach may thus replace invasive treatment methods in many patients.

Acne Vulgaris↗

PubMed1985

The effect of iontophoresis and vehicle pH on the in-vitro permeation of lignocaine through human stratum corneum.

The effect of iontophoresis and the pH of aqueous vehicles on the rate and extent of permeation of lignocaine through excised human stratum corneum was investigated. In the absence of iontophoresis, the rate of penetration was greatest at the higher pH values where lignocaine exists mainly in the unionized form; iontophoresis was most effective at the lower pH values where lignocaine is mainly ionized. At pH 3.4, and 5.2, the flux increased during iontophoresis, by approximately 8.5 and 4 times, respectively, relative to that occurring without iontophoresis. The present results suggest that some weak electrolytes which show poor percutaneous penetration may be administered topically using iontophoresis provided the drug is kept in a highly ionized form.

Humans↗

PubMed2004

Prostaglandins participate in the late phase of the vascular response to acetylcholine iontophoresis in humans.

The participation of prostaglandins (PGs) in the cutaneous vasodilatation to acetylcholine (ACh) applied via iontophoresis is under debate. Using laser Doppler flowmetry, we studied the long lasting effect (20 min) of iontophoretic application (30 s; 0.1 mA) of ACh on the human forearm. Experiments were repeated (1) using deionized water instead of ACh to test the effect of current application, (2) after scopolamine treatment to inhibit muscarinic cholinergic receptors, and (3) 2 h, 3 days and 10 days following inhibition of PG synthesis with aspirin or a placebo control. Cutaneous vascular conductance (CVC) was calculated at rest (CVC(rest)), at peak vasodilatation in the first 5 min following ACh iontophoresis (CVC(peak)), and 20 min after iontophoresis (CVC(20)). The minimal CVC (CVC(min)) following iontophoresis was also determined. Cutaneous response to ACh displayed a biphasic pattern with an early and transient peak (CVC(peak): 62 +/- 8% of the maximal CVC induced by local heating (MVC)) followed by a long lasting slower vasodilatation (CVC(min): 44 +/- 6; CVC(20): 56 +/- 5%MVC). The current itself had no major effect. Scopolamine almost abolished both phases. The long lasting phase was aspirin sensitive but not the transient phase. At hour 2 post-aspirin, CVC(peak) was 61 +/- 10, CVC(min) 26 +/- 6 and CVC(20) 29 +/- 6%MVC. At day 3, CVC(peak) was 53 +/- 9, CVC(min) 22 +/- 3 and CVC(20) 25 +/- 4%MVC. At day 10, CVC(peak) was 67 +/- 10, CVC(min) 47 +/- 7 and CVC(20) 50 +/- 8%MVC. Placebo had no effect. We conclude that PGs participate in the vasodilator response following ACh iontophoresis. Previous non-steroidal anti-inflammatory drug treatments must be taken into account when studying the effect of ACh iontophoresis.

Acetylcholine↗

PubMed2002

The effects of iontophoresis and electroporation on transdermal delivery of buprenorphine from solutions and hydrogels.

The in-vitro permeation of buprenorphine across skin was investigated to assess the effects of iontophoresis and electroporation on drug permeation from solutions as well as from hydrogels. Iontophoresis (0.3 mA cm(-2)) increased the buprenorphine permeation from solution by a factor of 14.27 as compared with passive diffusion; the application of electroporation increased the buprenorphine permeation from solutions by a factor of 8.45. The permeation experiments using cellulose membrane and stratum corneum (SC)-stripped skin as permeation barriers suggested that the enhancement with iontophoresis was primarily due to strong electrophoretic drift of buprenorphine molecules, whereas the enhancement seen with electroporation was mainly attributed to the creation of transient aqueous pores in the SC layer. Application of high-voltage pulses followed by iontophoresis resulted in a shorter permeation onset time from both solutions and hydrogels as compared with iontophoresis or electroporation alone. The charge repulsion between buprenorphine and chitosan vehicles as well as the competition effects of counter-ions for carboxymethylcellulose (CMC)-based polymers may account for the different permeation rates under electrical field. This study demonstrates the feasibility of using hydrogels for delivery of buprenorphine under the application of iontophoresis or electroporation, separately or together.

Administration, Cutaneous↗

PubMed1999

Skin pH changes associated with iontophoresis.

STUDY DESIGN: Randomized controlled trial. The researcher measuring skin pH was blinded to group assignment. OBJECTIVES: To compare the skin surface pH changes associated with iontophoresis. The investigation was designed to address the question of whether significant skin pH changes occur under the cathode on the skin surface when performing iontophoresis and assessed the influence of different electrode-buffering systems intended to stabilize skin pH (surface). BACKGROUND: Whether buffers are needed to stabilize skin pH during iontophoresis has not been thoroughly addressed in the literature. The effectiveness of immobile resins versus simple phosphate buffers is also unclear. METHODS AND MEASURES: Sixty volunteer subjects were administered iontophoresis of normal saline using buffered or nonbuffered electrode systems. Each subject participated in 1 of the 12 doses by electrode conditions (i.e., 5 subjects per group). Surface skin pH was measured before and after iontophoresis with a flat-surface pH electrode in concert with an analog pH meter. The independent variables were electrode type (4 levels) and dosage (3 levels). The dependent variable was the change in skin surface pH. RESULTS: A significant change in skin pH was found only when the treatment dose was 80 mA/minute with a nonbuffered electrode (x = 3.14 +/- 1.09). CONCLUSIONS: The skin pH changes that occur during a properly delivered iontophoresis treatment at dosages of 20 and 40 mA/min were small and not significantly different with or without the addition of buffers. Those pH changes associated with 80 mA/min doses were significantly greater when no buffer was employed but were stabilized by each of the buffers used in the study (preloaded immobile resins or simple phosphates added at point of treatment).

Adult↗

PubMed1989

Tobramycin iontophoresis into corneas infected with drug-resistant Pseudomonas aeruginosa.

Iontophoretic application of tobramycin was used to deliver drug to the cornea of rabbit eyes infected with a tobramycin-resistant strain of Pseudomonas aeruginosa (MIC = 31.25 micrograms/ml). Corneas infected with P. aeruginosa 27853/pMG6 were treated 22 hours after infection with tobramycin delivered by either iontophoresis, mock iontophoresis (eye cup without current), or application of fortified topical drops. Corneal iontophoresis of tobramycin at 25 mg/ml caused more than a three log reduction in bacteria; yielding a significantly lower number of bacteria compared to untreated controls and all other treatments (P less than or equal to 0.0001). Corneal iontophoresis of tobramycin at 10 mg/ml showed a one log reduction in the number of bacteria per cornea, yielding a significantly lower number of bacteria compared to untreated controls (P less than or equal to 0.0001), corneas treated with nine topical applications of 1.36% tobramycin drops (P less than or equal to 0.0001), and corneas treated with mock iontophoresis (P less than or equal to 0.02). These results suggest that iontophoresis is a powerful ocular delivery system for tobramycin and may be suitable for use with other chemotherapeutic agents.

Administration, Topical↗

PubMed2002

Effect of electroporation and iontophoresis on skin permeation of Defibrase--a purified thrombin-like enzyme from the venom of Agkistrodon halys ussuriensis Emelianov.

The purpose of this study was to investigate electroporation and iontophoresis as a means for in vitro delivery of Defibrase--a thrombin-like enzyme (TLE) from Agkistrodon halys ussuriensis Emelianov snake venom--through human epidermis membrane (HEM). Electroporation was carried out using an exponential decay pulse generator (BioR-ad Genepulser, USA) for a period of 0.5 h, followed by a period of 5.5 h passive diffusion or iontophoresis. The results indicated that the combined use of electroporation and anodal iontophoresis in pH 6.4 permeation medium could effectively enhance the skin permeation of Defibrase, whose apparent permeability coefficient was 1.6 +/- 0.8 x 10(-4) cm.h-1. The delivery of Defibrase by the combined use of electroporation and anodal iontophoresis was more effective than by electroporation alone (P < 0.01) or by the combined use of electroporation and cathodal iontophoresis (P < 0.01). Moreover, when the pH of the permeation medium was raised from 6.4 to 7.4 the permeation of Defibrase caused by a combined use of electroporation and anodal iontophoresis showed a tendency to increase. These results implied that electroosmotic flow effect might be important for the iontophoretic (following electroporation) skin permeation of Defibrase.

Batroxobin↗

PubMed2003

[Corneal graft rejection and corticoid iontophoresis: 3 case reports].

This is the first report of three cases of severe acute corneal graft rejection, treated by transscleral methylprednisolone (Solumédrol) iontophoresis. The efficacy of the treatment was evaluated by corneal transparency, visual acuity and corneal inflammation parameters. The patient was treated with Solumédrol iontophoresis once a day for 3 days with a topical corticotherapy reduced to three drops of dexamethasone per day. Iontophoresis was performed, under topical anesthesia, and lasted 3 minutes with a 1.5-mA current. The subjective and objective tolerance of iontophoresis was good. No side-effect was observed. Corneal transparency and visual acuity improved rapidly after the second iontophoresis procedure. These observations show that Solumédrol iontophoresis might be an alternative to pulse therapy in the treatment of corneal graft rejection. Further comparative studies are necessary to confirm these preliminary observations.

Adult↗

PubMed2005

Effect of iontophoresis on skin permeation of defibrase.

AIM: To investigate the effect of iontophoresis on skin permeation of defibrase. METHODS: Iontophoresis was carried out in side-by-side chambers, excised rat skin membrane (RSM) or human epidermis membrane (HEM). The effects of electrode polarity, permeation medium pH and ionic strength were evaluated. RESULTS: Permeation of defibrase caused by anodal iontophoresis was more effective [the apparent permeability coefficient was (1.2 +/- 0.4) x 10(-4) cm x h(-1)] than that of cathodal iontophoresis [(4.3 +/- 1.4) x 10(-5) cm x h(-1)]. The amount of permeated defibrase caused by anodal iontophoresis in pH 7.4 medium was (25 +/- 5) x 10(-14) mol x cm(-2), which was higher than that of in pH 6. 4 permeation medium [(15 +/- 4) x 10(-14) mol x cm(-2)]. CONCLUSION: Iontophoresis could enhance skin permeation of defibrase. Electroosmotic flow effect played an important role.

Animals↗

PubMed2004

Lidocaine iontophoresis versus EMLA cream for CO2 laser treatment in seborrheic keratosis.

BACKGROUND: Topical anesthesia for skin surgery has widely been used for a long time. Various preparations are used. The EMLA cream is the most popular one. OBJECTIVE: The authors compared the local analgesic effect of topical lidocaine iontophoresis and EMLA cream in a crossover study design. METHOD: After informed consent, 16 patients with seborrheic keratosis, who required CO2 laser surgery, were enrolled. Two lesions on the opposite side of the body with a comparable size, shape and location were selected from each patient. The lidocaine iontophoresis was done on one lesion and the EMLA cream was applied on the other The CO2 laser surgery was performed after 10 min of lidocaine iontophoresis and 60 min after EMLA cream. The level of pain was recorded using a 100-mm visual analog scale. Ratings of patient satisfaction were also assessed. RESULTS: There were no significant differences in pain scores between the two groups (p=0.968), but significantly higher in satisfaction scores (1-5 scale) in the iontophoretic group than the EMLA group (p=0.005). Fifteen patients preferred lidocaine iontophoresis (93.8%), none preferred EMLA cream. All patients in the present study tolerated the tingling and burning sensations. No severe adverse events and side effects were detected. CONCLUSION: Lidocaine iontophoresis provides effective pain relief for CO2 laser surgery of seborrheic keratosis as well as the EMLA cream. The effect is as fast as 10 min after application. There is no significant side effect. Most of the patients were satisfied. Lidocaine iontophoresis is a useful, noninvasive local anesthesia for CO2 laser surgery of superficial skin lesions.

Aged↗

PubMed2006

[Delivery of gentamicin to the rabbit eye using hydrogel and iontophoresis].

The aim of this study was to evaluate the use of solid hydrogel as a probe for the drug delivery to the rabbit eye upon application of low current iontophoresis. Hydroxyethyl methacrylate (HEMA), cross-linked with ethylenglycol dimethacrylate (EGDMA) were prepared to form solid hydrogels. The concentrations of gentamicin sulfate in different segments of rabbit eye after transconjunctival and transscleral iontophoresis were also studied. For iontophoresis we used a portable Mini Ion device (designed at Hebrew University of Jerusalem) and applied a current from 0 mA to 1.5 mA for pre-set period from 30 to 120 seconds and after application the concentrations of gentamicin in cornea were assayed. The rabbits in control group were treated with fortified gentamicin eye-drops (concentration 1.4 %). The highest concentration of gentamicin sulfate was reached after iontophoresis with current intensity of 1.5 mA applied for 60 s. High gentamicin concentration were found in the retina and in the sclera four hours after transscleral iontophoresis, the lowest concentration was obtained in vitreous. The delivery of gentamicin to the eye via iontophoresis with solid HEMA/EGDMA hydrogels seems to be promising method achieving high concentrations of the drug in the eye tissue.

Animals↗

PubMed1984

Iontophoresis of gentamicin into aphakic rabbit eyes. Sustained vitreal levels.

The authors evaluated the intraocular penetration of gentamicin (50 mg/ml) into aphakic rabbit eyes following anodal iontophoresis (0.75 mA for 10 min). Gentamicin levels were determined at 0.5, 4, 8, 16, and 24 hrs after iontophoresis (n = 6 eyes for each time) using an agar diffusion bioassay. Peak levels of 72.04 +/- 6.1 (means +/- SE) micrograms/ml for the corneas and 77.8 +/- 3.0 micrograms/ml for the aqueous humor were obtained at 30 min after iontophoresis. The peak vitreous level was 10.4 +/- 0.4 micrograms/ml, which was found at 16 hrs after iontophoresis. Therapeutic levels of 6.2 +/- 3.0 micrograms/ml were still present in the vitreous humor 24 hrs after iontophoresis. Iontophoresis appears to be an effective noninvasive method for delivering therapeutic levels of gentamicin into ocular tissues and fluids of the aphakic rabbit eye.

Animals↗

PubMed2002

[Transdermal delivery of diclofenac sodium gel after iontophoresis]

OBJECTIVE: To observe the in vivo effect of combined iontophoresis and laurocapram pretreatment on transdermal delivery of diclofenac sodium gel. METHODS: Diclofenac sodium gel was prepared using polyvinyl alcohol, carboxymethylcellulose sodium and hydroxypropylmethyl cellulose. The diclofenac blood level in rabbits was measured in four groups: passive diffusion, laurocapram pretreatment, iontophoresis (current density controlled at 0.3 mA/cm(2)) and combined laurocapram pretreatment and iontophoresis. Rabbit stratum corneum of each of the four groups was examined using a scanning electron microscope. RESULTS: Diclofenac blood concentration in the passive diffusion group was undetectable. The diclofenac blood concentration area under the curve compared with time was 8.4 &mgr;l ml(-1) h(-1) in the laurocapram pretreatment group, 2.7 &mgr;l ml(-1) h(-1) in the iontophoresis group and 15.4 &mgr;l ml(-1) h(-1) in the combination group. There was no detectable damage observed by scanning electron microscopyto the stratum corneum after iontophoresis or laurocapram pretreatment. CONCLUSION: The combination of iontophoresis and laurocapram pretreatment appears to enhance transdermal delivery of diclofenac sodium gel wi thout significant skin damage.

Journal Article↗