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Iontophoretic delivery of calcium for experimental hydrofluoric acid burns.

OBJECTIVE: To examine the efficacy of iontophoretic delivery of calcium to experimental hydrofluoric acid burns. DESIGN: Prospective, controlled study. SETTING: Institutional laboratory. SUBJECTS: Male nude rats. INTERVENTIONS: For the in vitro experiment, a full-thickness skin from the back was set in a vertical flow-through diffusion cell. Calcium chloride was applied to the donor chamber, and transdermal transport of calcium was examined with or without a voltage gradient of 1.5 V. Either intact skin or skin whose stratum corneum was stripped with adhesive tapes was used. For the in vivo experiment, hydrofluoric acid burns were induced by dispensing 50% hydrofluoric acid (50 microL) on the backs of the nude rats, who were under pentobarbital anesthesia. Rats were divided into four groups (n = 5 for each group): control group (burned but not treated); topical group (treated with calcium gluconate jelly); infiltration group (intradermal and subcutaneous injection of calcium gluconate); and iontophoresis group (treated with iontophoresis of calcium chloride at 1.5 V). Burn areas were measured and pathologic findings were classified microscopically into five stages at 1 wk: stage 1, epidermal burn; stage 2, superficial dermal burn; stage 3, deep dermal burn; stage 4, full-thickness burn; and stage 5, burn affecting the skeletal muscle. MEASUREMENTS AND MAIN RESULTS: In the in vitro experiment, calcium concentrations increased significantly only in stripped skins with a 1.5-V gradient. In the in vitro experiment, burn areas were reduced significantly in the iontophoresis group compared with the other three groups. Pathologic findings were significantly improved in the iontophoresis group compared with the control group. This efficacy of iontophoresis was observed when it was initiated within 30 mins after hydrofluoric acid burn. CONCLUSIONS: These results show that transdermal transport of calcium was enhanced in stripped skins by iontophoresis and that iontophoresis was more efficacious than topical or infiltration therapy for experimental hydrofluoric acid burns. Iontophoretic delivery of calcium seems to be easier than intra-arterial infusion and may be effective for the lesions where intra-arterial infusion is difficult.

Administration, Topical↗

Effects of iontophoretic versus injection administration of dexamethasone.

PURPOSE: Sixty-eight skeletally mature New Zealand white rabbits were used to study the effects of iontophoresis- and injection-delivered sodium phosphate dexamethasone (DX) on the morphologic, histologic, microscopic, and biomechanical properties of uninjured rabbit patellar tendons over an initial 14-d period. METHODS: Three control (untreated, placebo iontophoresis, and placebo injection) groups and two treatment (iontophoresis and injection) groups underwent serum, ELISA tendon, histology, electron microscopy, and biomechanical analysis. RESULTS: Serum DX levels were detectable and quantifiable in both treatment groups at 1 h but were significantly greater (P < 0.05) in the injected group (11.29 ng.mL-1) compared with the iontophoresis group (6.34 ng.mL-1). The most significant histologic finding was a lack of a cellular inflammatory response in the DX-treated groups at 24 h. Ultrastructural analysis produced no significant differences between size or size ratio of collagen fibrils among any groups. Morphologic examination revealed only injection puncture marks seen in appropriate tendons. Biomechanical testing produced disruption at the patellar insertion in 81% of the specimens. No injected tendon failed at the injection site. Normalized biomechanical properties included: 1) Stiffness increased in control and iontophoresis groups from 1 to 24 h, then gradually declined; the DX-injected specimens showed a similar but delayed effect. 2) Peak load at failure for iontophoresis and control groups was greatest at 24 h. The DX-injected group again showed a delayed response. 3) In general, total energy to failure revealed no significant differences between groups at any time period. CONCLUSION: It appears that iontophoresis or injection-delivered DX may produce anti-inflammatory effects without significantly altering ultrastructural or biomechanical characteristics of the rabbit patellar tendon within an initial 14-d period.

Analysis of Variance↗

Quantitation and kinetics of induced HSV-1 ocular shedding.

Iontophoresis of 6-hydroxydopamine (6-HD) to the rabbit eye, followed by topical instillation of 2% epinephrine, induces ocular shedding of herpes simplex virus type 1 (HSV-1) reliably and with a high frequency in latently infected rabbits. Rabbit eyes inoculated with HSV-1 (McKrae strain) showed dendritic lesions indicative of acute HSV infection and subsequently shed virus spontaneously at least once during days 20 to 39 postinoculation (P.I.). Two iontophoretic conditions were employed. Group A (3 rabbits, 60.3 days P.I.) received iontophoresis of 1.0% 6-HD at 0.75 mAmp for 3 min. Group B (three rabbits, 67.3 days P.I.) received iontophoresis of 0.1% 6-HD at 0.5 mAmp for 8 min. Following iontophoresis, 2% epinephrine was instilled topically once on the day of iontophoresis and twice daily for four consecutive days. Tear film was collected on Dacron swabs and titered on African green monkey kidney cells by a plaque assay procedure. In group A, 100% (6/6) of the eyes shed virus, and the average duration of shedding was 4.0 days. The titers ranged from 2.0 to 7.7 X 10(4) plaque-forming units (PFU) per eye. The highest daily average titer, 9.89 X 10(3) PFU/eye, occurred on day 5 following iontophoresis. In Group B, 100% (6/6) of the eyes also shed virus, and the average duration of shedding was 5.3 days. The viral titer of the tear film ranged from 5.0 to 1.4 X 10(5) PFU/eye. The highest daily average titer, 4.68 X 10(3) PFU/eye, also occurred on day 5 following iontophoresis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Iontophoretically applied potassium ions as an experimental pain stimulus for investigating pain mechanisms.

The present study investigated the psychophysical characteristics of potassium iontophoresis and its suitability as an experimental pain stimulus. Experiment 1 investigated the optimal duration of the pain stimulus for reliable reporting across repeated trials and whether the relationship between stimulus and subject response was linear, logarithmic, or a power function. In Experiment 2, the optimal interstimulus interval (ISI) was determined for reliable pain reporting, and stimulus history effects, both in terms of session effects and the effects of immediately preceding stimuli, were evaluated. In Experiment 3, potassium iontophoresis was compared with a sodium iontophoresis control. Linear functions described the stimulus-pain relationship best. No significant differences in the goodness-of-fit coefficients of determination, correlations, or coefficients of variation were found for the stimulus durations of 1, 2, and 4 sec. Significant stimulus history effects were found across a session, with adaptation and enhancement of responding for low- and moderate-intensity stimuli, respectively. The effects of the immediately preceding stimuli were suppression or enhancement of pain response, depending on the ISI, the preceding stimulus intensity, and the present stimulus intensity. Potassium iontophoresis was a significantly more effective pain stimulus than was sodium iontophoresis. It was concluded that potassium iontophoresis is a convenient and reliable experimental pain stimulus, which can be presented rapidly and repeatedly with minimal loss in consistency of subject pain report. Potassium iontophoresis provides a tool for investigating the neural modulation of pain in the relative absence of inflammation processes and tissue damage.

Adult↗

[An experimental study on physiotherapy for traumatic facial nerve injury].

OBJECTIVE: To investigate the effects of electric stimulation, iontophoresis and electric stimulation with iontophoresis therapy in treating traumatic facial nerve injury. METHODS: Fifty rabbits were used. All right buccal branch of facial nerve were injured. The rabbits were randomly divided into five groups and treated by different stimulation pattern: (a) electric stimulation group; (b) iontophoresis group; (c) iontophoresis with electric stimulation group; (d) routine therapy group; (e) control group. The histologic morphology, quantitative indices of nerve fibers and electroneurography(ENoG) indices were analyzed. RESULTS: (a) Iontophoresis with Vitamin B1 and Vitamin B12 improved the regeneration of facial nerve myelin sheath. And had the best effect among these groups. (b) Electric stimulation had great effect on axon regeneration. (c) The group of electric stimulation with iontophoresis therapy had the best comprehensive effect on the nerve injury. CONCLUSIONS: Both electric stimulation and iontophoresis have good effects on nerve regeneration, when they are used in combination, the best comprehensive effect will be expected.

Animals↗

Inhibitory effect of nitric oxide on neuronal activity in the periaqueductal grey matter of the rat.

Experiments were carried out in urethane-an-anesthetized rats to examine the effect of nitric oxide (NO) on neuronal activity within the dorsolateral sector of the midbrain periaqueductal grey matter (PAG), an area which is rich in NO-synthesizing neurones. NADPH-dependent diaphorase histochemistry revealed small NO synthase-containing perikarya, 15.4 +/- 3.1 microns (mean +/- SEM) in diameter, in a longitudinal column in the dorsolateral sector of the PAG. The labelled cell bodies were surrounded by a dense meshwork of stained fibres and processes in which unlabelled neurones were embedded. In order to establish whether NO was generated when NO donors were ejected iontophoretically from micropipettes, a chemiluminescence method was used to estimate the output of NO in vitro after iontophoresis of two chemically different classes of NO donor: the sydnonimine 3-morpholino-sydnonimin-hydrochloride (SIN 1) and the nitrosothiol S-nitroso glutathione (SNOG). Iontophoresis of both NO donors into 200 microliters aliquots of 165 mM NaCl using ejection currents between 6000 and 18,000 nA.min produced a current-related increase in the concentration of NO. Iontophoresis of SIN 1 in vivo produced a reproducible, current-related inhibition of firing in 40 of 59 neurones in the dorsolateral PAG. In 8 of 10 neurones the effect of SIN 1 was significantly reduced after iontophoresis of methylene blue (10-30 nA for 2.7-5 min). The inhibition took up to 7 min to develop and lasted for up to 13 min. Inhibitory responses to GABA were not affected by methylene blue. Iontophoresis of SNOG also inhibited ongoing activity of 18 of 24 neurones tested in the PAG. The experiments demonstrate firstly that NO donors can be used in vivo to deliver NO in the vicinity of neurones by iontophoresis from micropipettes. Secondly, NO appears to inhibit neuronal activity within the PAG.

Animals↗

Correlations between histamine-induced wheal, flare and itch.

Correlations between the skin reactions wheal and flare and the subjectively reported degree of itch were investigated in response to 1% histamine, intradermally applied by standardized skin prick and by iontophoresis. Experiments were performed with 15 male volunteers using a threefold repeated measures design (skin prick, and iontophoresis with 0.13 mA for 10 s and with 2.0 mA for 10 s). Skin reactions (perpendicular diameters) were determined at the time of their maximum (10 min). Itch was rated on a computerized visual analogue scale which was anchored upon the individual scratch threshold. Most effective in producing itch was the skin prick which caused strong sensations markedly above the scratch threshold during the entire period of measurement (30 min), whereas iontophoresis induced only transient itch sensations. On the other hand, the largest wheals were generated by iontophoresis of both intensities (mean 10 or 14 mm vs 6 mm with skin prick). The higher current induced higher itch, wheal and flare responses, but after eliminating this effect of stimulus intensity, no correlations were found. In contrast, skin prick-induced flare reactions varied with the degree of itch above the scratch threshold (r = 0.56; P < 0.01). Repeated measurements showed a higher stability for the itch reaction with skin prick compared with iontophoresis. It is hypothesized that in iontophoresis the brief (10-s) histamine bolus passed the most superficial pruritoceptive C fibres too quickly to induce long-lasting itch sensations, whereas the skin prick caused a deposit at the dermal-epidermal junction releasing histamine during the entire time of measurement. Consequently, both the C fibre-mediated itch and the axon reflex flare were more pronounced with the skin prick, and the wheal resulting from a permeability increase in the postcapillary venule walls was an independent phenomenon.

Adult↗

The induction of serotonin3-like receptor supersensitivity and dopamine receptor subsensitivity in the rat medial prefrontal cortex after the intraventricular administration of the neurotoxin 5,7-dihydroxytryptamine: a microiontophoretic study.

This study examines the effect of intraventricular administration of the neurotoxin 5,7-dihydroxytryptamine on serotonin1A, serotonin2 and serotonin3 receptors in the rat medial prefrontal cortex using in vivo extracellular single cell recording and iontophoresis. Iontophoresis of the serotonin1A, serotonin1C,2 and serotonin3 receptor agonists (+-)-8-hydroxy-(di-n-propyl)aminotetralin, (+-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane and 2-methylserotonin, respectively, produces a current-dependent (5-80 nA) suppression of the basal firing rate of medial prefrontal cortical cells in sham- and 5,7-dihydroxytryptamine-lesioned rats. The suppression produced by 2-methylserotonin and serotonin was significantly greater in 5,7-dihydroxytryptamine-lesioned rats than in control rats. No significant difference in the spontaneous activity of medial prefrontal cortex cells was observed between experimental and control rats after iontophoresis of (+-)-8-hydroxy-(di-n-propyl)aminotetralin or (+-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane. There was no significant difference between the groups regarding the response of medial prefrontal cortex cells to the iontophoresis of GABA, whereas the response of medial prefrontal cortex cells to the iontophoresis of dopamine was significantly attenuated in animals pretreated with 5,7-dihydroxytryptamine compared to controls. Our results indicate that 5,7-dihydroxytryptamine-induced denervation selectively enhances the sensitivity of serotonin3-like receptors in the medial prefrontal cortex, which could, at least partially, account for the serotonin denervation supersensitivity. Moreover, the finding that the response of medial prefrontal cortical cells to the iontophoresis of dopamine is attenuated in 5,7-dihydroxytryptamine pretreated rats is consistent with the view that the inhibitory action of dopamine in the medial prefrontal cortex is dependent upon serotonin tone.

5,7-Dihydroxytryptamine↗

Visualization studies of human skin in vitro/in vivo under the influence of an electrical field.

The aim of this study was to investigate the local changes in the ultrastructure of human skin after iontophoresis, using cryo-scanning, transmission and freeze fracture electron microscopy in human skin in vitro and in vivo. Human dermatomed skin was subjected to passive diffusion for 6 hours followed by nine hours of iontophoresis at 0.5 mA/cm2. The skin was processed and examined using both cryo-scanning electron microscopy (Cryo-SEM) and transmission electron microscopy (TEM). In addition, iontophoresis patches were applied to healthy volunteers for 3.5h with 0.5h of passive delivery followed by 3h of iontophoresis at a current density of 0.25 mA/cm2. Subsequently, a series of tape stripping were performed, which were visualized by freeze fracture transmission electron microscopy (FFTEM). In vitro, the cryo-scanning electron microscopy study revealed that electric current induced changes in the water distribution in the stratum corneum. Transmission electron microscopy showed no local changes in the ultrastructure of the stratum corneum; however, layers of detached corneocytes were frequently observed especially at the anodal site. In vivo, there was no evidence of perturbation of the stratum corneum lipid organization; however, changes in the fracture were noticed deeper in the stratum corneum at the anodal side, indicating a weakening of the desmosomal structure. The in vitro/in vivo studies suggest that iontophoresis results in the formation of intercellular water pools (in vitro observation) and a weakening of the desmosomal structure (in vivo observation) only in the upper part of the stratum corneum. However, no changes in the lipid organization were observed in vitro and in vivo at the current densities of 0.5 and 0.25 mA/cm2, respectively. Therefore, even at relatively high current densities, no drastic changes in the ultrastructure of the stratum corneum are observed. As far as structural changes in stratum corneum are concerned iontophoresis is therefore a safe method at the experimental conditions we used.

Adult↗

Factorial design approach to evaluate interactions between electrically assisted enhancement and skin stripping for delivery of tacrine.

The objective of this work was to study the mechanisms of action of iontophoresis and electroporation and their interaction effects on delivery of tacrine hydrochloride in vitro across intact and stripped rat skin. Experiments were done according to a full factorial design, to quantify the effects of iontophoresis (X1), electroporation (X2) and stripped skin (X3) alone and in combination on cumulative drug delivery at 6 h. Mathematical model eliciting the main effects of the factors and their interaction on cumulative tacrine delivery in 6 h shows that all three techniques examined alone have a positive impact on the permeation of tacrine, the greatest enhancement in delivery achieved by iontophoresis. However, iontophoresis in combination with electroporation or skin stripping yielded no improvement in delivery compared to iontophoresis alone. The most significant enhancement is seen when all three methods of assisted delivery are done in combination. Iontophoresis appears to control drug delivery to the exclusion of other enhancement methods. Electroporation appears to cause formation of a large depot of tacrine in the skin.

Animals↗

Assessment of microvascular function by study of the dose-response effects of iontophoretically applied drugs (acetylcholine and sodium nitroprusside)--methods and comparison with in vitro studies.

Current knowledge about vascular function stems mainly from pharmacological in vitro studies using mounted vascular strips on a strain gauge. We know of no paper that has systematically examined the possibility of assessing the conventional dose-response effects of iontophoresis and laser Doppler investigation of vasoactive substances and compared those relations to data obtained from strips mounted on a strain gauge. We used the vasoactive substances acetylcholine (endothelium dependent) and sodium nitroprusside (endothelium independent) and an antagonist (atropine) to enable further investigations in the receptor physiology of iontophoresis. Dose-response curves from the iontophoresis experiments showed close similarity to those obtained by vascular strips mounted on a strain gauge. The coefficient of variation (CV) of the dose-response factors found in iontophoresis (both inter and intra experimental variability) was low. The iontophoretic effective dose of 50% (ED50) for acetylcholine and nitroprusside had only CVs of 25% and 26%, respectively, compared with 71% and 77% for the vascular strips. Acetylcholine-induced response was antagonized by iontophoresis of atropine. Contrary to expectations, this antagonism was not competitive. The results show that iontophoresis in combination with laser Doppler technology produces reproducible and reliable dose-response curves that picture the vascular effects of vasoactive drugs.

Acetylcholine↗

Enhancement of thermal hyperalgesia by alpha-adrenoceptors in capsaicin-treated skin.

This study aimed to investigate whether the endogenous release of noradrenaline would influence hyperalgesia to heat in skin sensitized by the topical application of 0.6% capsaicin. To release endogenous stores of noradrenaline, tyramine was introduced transcutaneously by iontophoresis into the volar aspect of the forearm of 19 healthy subjects. The heat pain threshold fell from 43.7 +/- 3.8 degrees C to 41.3 +/- 4.0 degrees C after the iontophoresis of tyramine in capsaicin-treated skin (P < 0.001), but did not change significantly after tyramine iontophoresis in untreated skin. The heat pain threshold decreased by 0.5 +/- 2.2 degrees C after the iontophoresis of saline, indicating that nonspecific factors did not fully account for the hyperalgesic effect of tyramine. Iontophoresis of the alpha-adrenergic antagonist, phenoxybenzamine, after the capsaicin treatment blocked the hyperalgesic effect of tyramine, suggesting that thermal hyperalgesia was mediated by alpha-adrenoceptors. However, iontophoresis of phenoxybenzamine before the capsaicin treatment was ineffective. These findings suggest that release of endogenous stores of noradrenaline increases sensitivity to heat in skin sensitized by capsaicin. In addition, neurogenic inflammation appears to increase access to the receptors that facilitate thermal hyperalgesia.

Administration, Topical↗

Distribution and quantification of polyethylenimine oligodeoxynucleotide complexes in human skin after iontophoretic delivery using confocal scanning laser microscopy.

Iontophoresis may be a potentially useful technique for the delivery of oligonucleotides into the skin. To enhance intracellular uptake during iontophoresis, we investigated the dermal delivery of oligodeoxynucleotides (ODN) as a polyelectrolyte complex with polyethylenimine (PEI). Perpendicular cross-sectioning was performed to visualize and quantify the penetration properties of double labeled PEI/ODN complexes across full thickness human skin. Due to the net positive charge of the complexes, anodal iontophoresis was expected to enhance skin delivery by electrorepulsion compared to passive diffusion. Confocal laser scanning microscopy demonstrated that non-complexed ODN could penetrate the skin after 1 h of cathodal iontophoresis but not by passive diffusion or anodal iontophoresis. However, extensive degradation occurred as documented by a dramatic decrease of fluorescence intensity within viable skin tissue after 10 h. Anodal iontophoresis of the complexes led to a deep penetration of both the TAMRA-labeled ODN and the Oregon Green-labeled PEI. A constant increase in fluorescence indicated a protective effect of the polymer against nuclease degradation. Co-localization of red and green fluorescence was noted within numerous nuclei of epidermal keratinocytes. In contrast, passive diffusion of the complexes did not lead to successful uptake into keratinocytes and was limited to the stratum corneum. Complexation of ODN by PEI, therefore, seems to be a promising method to enhance both the transport of charged complexes into the skin and to facilitate intracellular uptake, which may potentially be useful for the local treatment of skin diseases using ODN.

Drug Carriers↗

The effect of electroporation on iontophoretic transdermal delivery of calcium regulating hormones.

Electrically-assisted delivery by iontophoresis and/or electroporation was used in vitro to deliver the calcium regulating hormones, salmon calcitonin (sCT) and parathyroid hormone (1-34) (PTH) through human epidermis. Such delivery could be useful for chronic treatment of post-menopausal osteoporosis and other clinical indications as a superior alternative to parenteral delivery. sCT (50 microg/ml) or PTH (1-34) (100 microg/ml) formulation was prepared in citrate buffer (pH 4.0 or 5.0, respectively). Epidermis separated from human cadaver skin was used. Iontophoresis was applied using a constant current power source and electroporation with an exponential pulse generator. Silver/silver chloride electrodes were used. A combination of electroporation and iontophoresis resulted in higher transdermal permeation than either one technique alone. Electroporation also shortened the lag time of iontophoretic transdermal delivery of salmon calcitonin. Pulsing at lower voltages followed by iontophoresis did not result in increased transport (over iontophoresis alone), perhaps because the transdermal voltage was very low. The transdermal transport of salmon calcitonin by pulsing with 15 pulses (1 ppm) of 500 V (200 ms) followed by iontophoresis led to a quick input and high flux. The average transdermal voltage was only about 50 V for a 500 V study.

Administration, Cutaneous↗

Transdermal iontophoretic delivery of timolol maleate in albino rabbits.

The use of transdermal iontophoresis is a promising technique for the systemic delivery of water soluble and ionic drugs of relatively large molecular size. The present study investigates the skin pre-treatment with Azone (laurocapram) and iontophoresis on the pharmacodynamic effect of timolol maleate (TM) in vivo in albino rabbits. The pharmacodynamic effect of TM was evaluated by transdermal delivery and compared with an intravenous (i.v.) administration. Iontophoresis of TM (0.1 mg/ml) produced a significant inhibition in the isoprenaline (ISP)-induced tachycardia. Iontophoresis with higher concentration of TM (1 mg/ml) produced a 100% inhibition of the ISP induced tachycardia. Pre-treatment of skin with Azone (3% v/v emulsion) eliminated the lag time and prolonged the duration of action of iontophoresis from 4 to 6 h. The AUC of Azone treated group was significantly higher than that of the untreated group (P<0.05). Further, the AUC with iontophoretic delivery and pre-treatment of Azone was comparable to that of intravenous TM (30 microg/kg). In conclusion, iontophoresis in combination with Azone can increase the transdermal delivery of TM, whereby the required transport rate can be achieved with a lower drug concentration.

Administration, Cutaneous↗

Role of appendages in skin resistance and iontophoretic peptide flux: human versus snake skin.

PURPOSE: 1. The assessment of the role of hair follicles and sweat glands in skin resistance and percutaneous iontophoretic flux of 9-desglycinamide, 8-arginine vasopressin (DGAVP) by comparing two skin species: human stratum corneum which contained hair follicles, sweat and sebaceous glands, and shed snake skin which lacked all appendages. 2. The effect of 1-dodecylazacycloheptan-2-one (dodecyl-Azone, a lipid perturbing agent) on the iontophoretic DGAVP flux. METHODS: Iontophoresis in vitro was performed in a transport cell (0.79 cm2 area available for percutaneous transport) by 8-hours application of a pulsed constant current of 100 Hz, 50% duty cycle and 0.26 mA.cm-2 current density delivered by a pair of Ag/AgCl electrodes, of which the anode was facing the anatomical surface of the skin samples. RESULTS: The initial resistances of human stratum corneum and shed snake skin samples were of the same order of magnitude (20-24 k omega.cm2) and both skin species showed a comparable resistance-decrease profile during 8-hours iontophoresis, indicating that the resistances were mainly determined by the stratum corneum and not greatly influenced by the appendageal structures. The initial resistances of the skin samples pretreated with dodecyl-azone were less than 50% of the values of untreated samples. Because dodecylazone is known to perturb the ordering of the intercellular lipids, the effect of azone on the resistance confirms that the resistance mainly resides within the intercellular lipids of the stratum corneum. No correlation was found between the iontophoretic DGAVP-flux and the conductance of human skin. For shed snake skin, however, a good correlation was found, indicating that the iontophoretic permeability of human skin in vitro for a peptide such as DGAVP is, unlike shed snake skin, not related to its overall permeability to ions. While the initial resistances of both human and snake skin were in the same order of magnitude and showed the same declining profile during iontophoresis, the steady state iontophoretic DGAVP flux across human stratum corneum was approximately 140 times larger than through shed snake skin. These findings suggest that small ions follow pathways common to both skin types, presumably the intercellular route, while the peptide on the other hand is transported differently: across snake skin presumably along intercellular pathways only, but across human stratum corneum along additional pathways (most likely of appendageal origin) as well. This interpretation is supported by the observations made of the effects of dodecyl-azone on DGAVP-iontophoresis. Pretreatment with dodecyl-azone did not significantly change steady state fluxes and lag times of DGAVP-iontophoresis across human stratum corneum, but resulted in a significant 3-fold lag time decrease and a 3-fold flux increase of DGAVP-iontophoresis across snake skin. CONCLUSIONS: The results of these in vitro studies emphasize the importance of the appendageal pathway for iontophoretic peptide transport across human stratum corneum.

Adult↗

Facilitation of iontophoretic drug delivery through intact and caries-affected dentine.

AIM: To investigate the facilitative role of iontophoresis in drug delivery through intact and caries-affected dentine into the pulp. METHODOLOGY: Forty-eight intact dentine or caries-affected dentine discs were prepared from freshly extracted human third molars. The hydraulic conductance was measured before and after the experiments. Drug diffusion with and without iontophoresis (0.05 mA, 10 min) was evaluated using a split-chamber device. The enamel side chamber was filled with metronidazole (MN), sodium salicylate (SS) or naproxen sodium (NA), while the pulpal side was circulated with phosphate buffered saline (PBS) and pressurized (15 cmH2O). Samples were collected after 1 h. Drug concentrations of the pulpal side solution were determined using a spectrophotometer. Then, electrical impedance of each dentine disc was measured. Finally, the dentine disc surfaces were observed by scanning electron microscopy. RESULTS: Drug diffusion was significantly influenced by iontophoresis, caries-induced changes in dentine and the drugs used (three-way anova, P < 0.05). The diffusion of all the drugs through caries-affected dentine was significantly less than that through intact dentine (independent t-test, P < 0.05). Also, iontophoresis facilitated the diffusion of all the drugs through intact and caries-affected dentine. The drug diffusion of SS was significantly higher than MN and NA (one-way anova, P < 0.05), independent of iontophoresis. CONCLUSIONS: Presence of dental caries may inhibit drug diffusion through dentine into the pulp. However, iontophoresis could enhance the delivery of ionized drugs through both intact and caries-affected dentine.

Adult↗

Comparing two methods of topical anesthesia used before intravenous cannulation in pediatric patients.

INTRODUCTION: The purpose of this study was to compare the efficacy of two methods of topical anesthesia before venipuncture or intravenous cannulation of pediatric patients to assess which type of topical anesthetic would better alleviate pain in the least amount of time with the greatest success rate of cannulation. METHODS: This study was a randomly controlled trial of 100 preoperative pediatric patients aged 5 to 21 years. The following methods of topical anesthesia were compared: (a) iontophoresis of a topical solution of 2% lidocaine with epinephrine 1:100,000 using a Phoresor Dose Controller (PDC) with Numby Stuff electrodes and a eutectic mixture of local anesthetic and (b) 2.5% lidocaine and 2.5% prilocaine (eutectic mixture of local anesthetics [EMLA] cream). RESULTS: Children reported less pain with iontophoresis (M = 0.08) compared with EMLA cream (M = 1.88, P < .001). Time to accomplish topical anesthesia was shorter with iontophoresis (13 minutes) compared with EMLA cream (60 minutes, P < .001). Failure to accomplish venipuncture occurred 5 times with the iontophoresis method and 8 times with the EMLA method (not significant). No dermal burns resulted from use of iontophoresis. DISCUSSION: We conclude that use of iontophoresis in pediatric patients is safe, rapid, and significantly more effective than is EMLA cream in reducing pain associated with venipuncture or intravenous cannulation.

Administration, Topical↗