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The distribution of metallic constituents in dentin subjected to iontophoresis.

The concentration gradient and distribution of a metallic constituent in dentin which has been subjected to iontophoresis, using a water solution of silver diamine hydroxide and zinc chloride, were analyzed by means of EPMA as a basic study for pulp capping or cavity lining. Line scanning analyses parallel to the tooth axis showed that the transportation distance of metallic ions depends strongly on potential, period of iontophoresis and structural differences in dentin. Although metallic silver or zinc was found in the dentinal tubules, there was one case in which no metal was observed. The change in the distribution can be described as power function.

Calcium↗

Clinical use of iontophoresis to treat facial pain.

Iontophoresis is a modality that assists with the entry of certain therapeutic medications into injured sites. Medications, such as anesthetics, vasoconstrictors, and some corticosteroids, when dissolved in water, separate into positive and negative ions. When an electric current is passed through an ionized solution, the ions of these agents carry the electric current from the positive to the negative electrode. The above medications have been shown to be beneficial in the treatment of TMD. These agents in liquid form are placed in meditrode pads that are attached to skin or mucosal surface over the sites that are to be treated. The treating (active) meditrodes and a larger ground (dispersive or return) meditrode are attached to an iontophoretic unit by wire leads to form a closed circuit. With iontophoresis, the treating medications can be placed in the target areas in high concentrations.

Analgesics↗

Non-invasive assessment of the effects of iontophoresis on human skin in-vivo.

The stratum corneum (SC), the outermost layer of the skin, presents a formidable barrier to transdermal drug delivery. As a result, different strategies have been developed to enhance drug transport into and through skin. Iontophoresis involves the application of a small electrical current which drives molecules across the skin and controls relatively well the rate of delivery. Although the technique has been widely investigated in-vitro, the evaluation of skin integrity in-vivo after iontophoresis is absolutely necessary for the future clinical application of this approach. This paper reviews the non-invasive biophysical techniques which have been used to assess the effects of current application on human skin in-vivo. Specifically, transepidermal water loss, infrared spectroscopy, impedance spectroscopy and skin blood flow measurements are discussed. After first presenting the basic principles of these methods, their application to the determination of SC barrier function and skin integrity is addressed, and the criteria for selecting the most appropriate approach are considered.

Administration, Cutaneous↗

Safe and efficient transdermal delivery of desmopressin acetate by iontophoresis in rats.

Iontophoretic delivery of desmopressin acetate (DDAVP) was assessed for delivery efficiency and drug stability, both in vitro and in vivo. The effect of current intensity and duration of current application on the decomposition of DDAVP was investigated in vitro. It was shown that when a current of 0.1 mA was applied for 5 min, the decomposition of DDAVP was negligible. In vivo experiments under the same conditions showed that the antidiuretic response to DDAVP persisted for about 6 h. Furthermore, when this iontophoresis was repeated 3 times at intervals of 4 h, the antidiuretic response persisted for about 11 h. These results suggest that repeated short-term iontophoresis is a safe and effective technique for transdermal delivery of DDAVP.

Administration, Cutaneous↗

Transfer of diclofenac sodium across excised guinea pig skin on high-frequency pulse iontophoresis. II. Factors affecting steady-state transport rate.

Some of the factors affecting the steady-state transport rate of diclofenac sodium across excised guinea-pig skin during high-frequency pulse iontophoresis were examined. The same mathematical expression was employed for enhancement ratio as a function of applied voltage as the one derived for direct-current iontophoresis. The effective voltage drop across the skin was only 1.1% of the applied voltage. The steady-state flux value increased with increase of the donor concentration.

Animals↗

Transtympanic iontophoresis: personal experience.

After having described the method of application used for iontophoresis and the results of previous studies carried out by other authors in the hope of finding a definite use for its clinical application, the authors present their personal experience carried out with the use of various chemical substances applied to both the guinea pig and to man. The chemicals taken into consideration were those used in the treatment of otitis media: anti-inflammatory, antibiotic, and mucolytic products. Iontophoresis proved to be a simple and effective method for the treatment of certain middle ear diseases, and offered a more rapid recovery in comparison with subjects treated uniquely by traditional methods.

Acetylcysteine↗

Gentamicin iontophoresis in the treatment of bacterial otitis externa in the guinea pig model.

Pseudomonas otitis externa is one of the most common infections treated by otolaryngologists. Infections induced in 30 guinea pigs appeared similar to that seen in humans. The ears were then placed into four treatment groups: group A, which received a single cleaning; group B, which received a single cleaning followed by gentamicin drops 4 times daily; group C, which received a single cleaning followed by a single gentamicin iontophoresis treatment; and group D, the control group, which received no treatment. Infections were analyzed by grading edema, purulence, and erythema. An average of 10.2 days was required for control group to return to normal appearance. Groups A, B, and C had mean resolution times of 5.9, 4.7, and 4.3 days, respectively. Gentamicin iontophoresis appears to be promising, with results as good as drop therapy in otitis externa in the guinea pig model.

Animals↗

Transdermal iontophoresis. Part II: Peptide and protein delivery.

The advent of sophisticated biotechnological processes has generated an interest in peptide and protein pharmaceuticals. However, the rapid developments in biotechnology are not matched by the developments in the delivery of these molecules. Presently, most of the peptides and proteins are delivered by parenteral route due to their poor oral bioavailability. The inherent discomforts associated with the parenteral therapy has prompted investigations into other nonparenteral routes and drug delivery techniques. Transdermal iontophoresis is one such technique showing good promise in the controlled and enhanced delivery of peptides and proteins. It offers noninvasive, continuous, pulsatile delivery as well as preprogramed complex dosing regimens. Miniature battery powered and wearable patches for peptides and proteins are expected to be on the market by the turn of this century. In continuation of our earlier review, this review explores the potential of transdermal iontophoresis for the delivery of peptides and proteins with the main focus on the suitability of the technique along with the factors to be considered in the design of this drug delivery system and its future prospects.

Administration, Cutaneous↗

Transport numbers in transdermal iontophoresis.

Parameters determining ionic transport numbers in transdermal iontophoresis have been characterized. The transport number of an ion (its ability to carry charge) is key to its iontophoretic delivery or extraction across the skin. Using small inorganic ions, the roles of molar fraction and mobility of the co- and counterions present have been demonstrated. A direct, constant current was applied across mammalian skin in vitro. Cations were anodally delivered from either simple M(+)Cl(-) solutions (single-ion case, M(+) = sodium, lithium, ammonium, potassium), or binary and quaternary mixtures thereof. Transport numbers were deduced from ion fluxes. In the single-ion case, maximum cationic fluxes directly related to the corresponding ionic aqueous mobilities were found. Addition of co-ions decreased the transport numbers of all cations relative to the single-ion case, the degree of effect depending upon the molar fraction and mobility of the species involved. With chloride as the principal counterion competing to carry current across the skin (the in vivo situation), a maximum limit on the single or collective cation transport number was 0.6-0.8. Overall, these results demonstrate how current flowing across the skin during transdermal iontophoresis is distributed between competing ions, and establish simple rules with which to optimize transdermal iontophoretic transport.

Administration, Cutaneous↗

Enhanced delivery of 5-aminolevulinic acid esters by iontophoresis in vitro.

The goals of this study were to quantitatively evaluate the iontophoretic delivery of a homologous series of cationic aminolevulinic acid (ALA) esters and to determine the contributions of electromigration and electroosmosis to their overall electrotransport in vitro. Anodal iontophoretic transport of ALA esters through porcine skin in vitro was followed for 2 h at a constant current of 0.5 mA/cm2. To deduce the mechanism, the concomitant transport of an electroosmotic marker, mannitol, was also assessed. Positively charged ALA esters of moderate lipophilicity showed increased iontophoretic flux through the skin. A more than 50-fold enhancement as compared with the zwitterionic parent ALA was observed for the methyl ester. As the size and lipophilicity of the ester increased, the efficiency of electrotransport decreased. The most lipophilic esters reduced the electroosmotic flow presumably because of the association of these cations with negative charges in the skin. Iontophoresis of methyl-ALA and hexyl-ALA also increased the amount of prodrug delivered into the skin. In summary, significant topical delivery of ALA esters can be achieved by iontophoresis, and transport into and across the skin was greatly enhanced compared with that of ALA itself. It remains to be seen whether this enhanced local bioavailability of the protoporphyrin prodrug can allow improved photodynamic therapy for the treatment of skin cancer.

Aminolevulinic Acid↗

The effectiveness of sodium fluoride treatment with and without iontophoresis on the reduction of hypersensitive dentin.

The effectiveness of topical sodium fluoride applied with and without iontophoresis was compared in patients complaining of tooth hypersensitivity. Reduction of sensitivity to cold and mechanical stimuli was evaluated during a period of 8 months by pain scoring in the exposed cervical dentin of homologous teeth on the two sides of the jaws. There was a significant decrease in the sensitivity of the exposed cervical dentin after treatment with sodium fluoride solution, with or without iontophoresis, during the whole experimental period. There was no striking difference between the two forms of treatment with respect to the reduction of sensitivity to mechanical and cold stimuli.

Adult↗

[Fundamental study of a local drug delivery system by means of intracanal medication. Influence of iontophoresis on the periphery of the root surface].

The purpose of this study was to evaluate a new system of drug delivery to periodontal pocket by means of intracanal dressing and additional iontophoresis in vitro. Forty extracted human teeth with a single root were used. After the root canal was prepared endodontically, the periphery root apex was painted with the Silux system (3 M Co.) to close the apical foramen. Each tooth was planted into an agar block. Three drugs (zinc iodide-iodine, penicillin G. potassium, minocycline HCl) were used (Table 1), and 50 microliters of each drug was injected into an individual root canal. Then a cathodic current (3 mA x 40 min) was applied using an automatic current volte regulater (PAV-200, Jooko Co.) with a platinum wire electrode inserted in the root canal (Fig. 1). The degree of drugs diffusion in the agar around teeth was estimated by individual color reactions zinc iodide-iodin test for starch, penicillin G. potassium test for phosphomolybdic acid, minocycline HCl test for ferric chloride). And also, the effects of root planing and etching by Quick Jet (Yosida Co.) on the root surface were evaluated in the same way. The results were as follow: 1. The degree of diffusion by intracanal electrical medication was greater in the cervical third area than the middle and apical third. 2. Several small areas stained by the iodo-starch color reaction were observed around the cervical root surface where greater diffusion was observed. 3. Many dentinal tubules were observed on a limited root surface where root planing and Quick Jet, were employed caused greater diffusion. 4. The results suggest the new delivery system for management of the microorganisms by intracanal medication and additional iontophoresis.

Humans↗

Corneal nerves contain intra-axonal HSV-1 after virus reactivation by epinephrine iontophoresis.

Experimental ocular models of herpes simplex virus type 1 (HSV-1) reactivation have been used to monitor viral shedding in the tear film and the appearance of corneal epithelial lesions, but the temporal correlation between reactivation and the presence of viral particles in the corneal nerves has not been made. Two New Zealand white rabbits were inoculated with 20 microliters of HSV-1 McKrae strain (5.0 x 10(6) PFU/ml) in each eye. Beginning on postinfection day 82, ocular iontophoresis (0.8 mAmps for 8 min) of 0.01% epinephrine was done once a day for 3 consecutive days to induce reactivation. Ten limbal nerves from four corneas processed for transmission electron microscopy contained 883 unmyelinated and 40 myelinated axons. Seven nerves were positive for virus. Viral particles were found only in unmyelinated axons, and in low frequency (24/883). Virus was not found in Schwann cells, perineurium, or adjacent stroma nor were virus particles seen exiting axons. No enveloped virions were found. Axons from six nerves of four control corneas from rabbits with latent, but not reactivated, HSV-1 did not contain virus particles. Induction by corneal iontophoresis of epinephrine suggests that HSV-1 is translocated from the ganglion to the cornea through axonal transport mechanisms. For the first time, evidence of anterograde, intra-axonal transport of HSV-1 particles in response to epinephrine reactivation is demonstrated.

Animals↗

The effect of alpha blockade on iontophoresis-induced ocular shedding of latent HSV-1 W in different host animals.

Previous studies demonstrated that non-specific beta blockade promoted ocular shedding of latent HSV-1 in the mouse and rabbit iontophoresis models. The present study examined the effect of topical alpha blockers, thymoxamine and corynanthine, on reactivation and induced ocular shedding of latent HSV-1 W in different host animals. Latent trigeminal ganglionic infection was established in Balb/c mice and New Zealand rabbits following corneal inoculation with HSV-1 W strain, and later confirmed by co-cultivation. Treatment with coded eye drops (thymoxamine, corynanthine or BSS was begun one day prior to iontophoresis induction and continued BID OU for 5 days. Reactivation and recovery of latent HSV-1 was determined by daily ocular swabs, and characteristic HSV-1 cytopathic effect in Vero cells. In Balb/c mice, topical administration of thymoxamine 0.5% or corynanthine 5% significantly reduced the number of virus-positive eyes, virus-positive mice, and total virus-positive swabs per experiment, whereas the inhibitory effect was minimal in NZ rabbits. We conclude that alpha blockade may alter the reactivation signal that is mediated via the adrenergic system, and that different host factors (as expressed in different species) may play an important role in this process.

Administration, Topical↗

Vanadate promotes reactivation and iontophoresis-induced ocular shedding of latent HSV-1 W in different host animals.

Vanadate is a potent inhibitor of calcium stimulated ATPase, Na, K-ATPase, and may have adrenergic activity. Using the iontophoresis method, we compared vanadate to a BSS control and the standard iontophoresis model (6-hydroxydopamine/epinephrine) by measuring induced ocular shedding of latent HSV-1 in different host animals. Latent trigeminal ganglionic infections were established in Balb/c mice and New Zealand rabbits following corneal inoculation with HSV-1 [W] strain, and later confirmed by cocultivation. Latently-infected animals (greater than 1 month post-infection) were divided into three treatment groups. Each group was iontophoresed with BSS, vanadate 1% or 6-HD 1%, and then treated topically for 10 days with BSS, vanadate or epinephrine respectively. Reactivation and recovery of latent HSV-1 was detected by daily ocular swabbing, plating, and observing progressive viral growth in Vero cells. The vanadate group had more virus-positive eyes than the BSS control group in mice, (8/32 vs. 1/32 P less than .01), and also in rabbits (14/20 vs 6/22 P less than .01). Virus-positive animals and total positive swabs were also higher for vanadate than BSS in both mice and rabbits. Furthermore, while vanadate was associated with fewer virus-positive eyes than 6-HD & EPI (8/32 vs. 17/32 P less than .02) in mice, there were no significant differences in rabbits. We conclude that vanadate promotes ocular shedding of latent HSV-1, and may act through an adrenergic mechanism.

Animals↗

Insulin iontophoresis in cystic fibrosis.

Insulin and its vehicle without insulin were administered separately by iontophoresis to patients with cystic fibrosis (CF), obligate heterozygotes, and healthy controls. The resultant sweat chloride concentration after treatment with both preparations was compared in each individual. No difference after the two treatments was found in the control sample. A decrease in sweat chloride concentration after insulin iontophoresis in comparison with the vehicle was observed in both the CF (P smaller than 0.005) and heterozygote (P smaller than 0.01) samples. These observations suggest an involvement of insulin in CF and a possible role of insulin in sweat gland function.

Chlorides↗

Iontophoresis in dermatology.

Iontophoresis is the process of increasing the penetration of drugs into the skin by application of an electric current. The drug is applied under an electrode of the same charge as the drug, and a return electrode opposite in charge to the drug is placed at a neutral site on the body surface. Electrical energy assists the movement of ions across the skin using the principle "like charges repel each other and opposite charges attract". In this article, we discuss the mechanism, principles, factors influencing iontophoresis and its application for various dermatological conditions.

Administration, Topical↗

Iontophoresis: noninvasive drug delivery.

Iontophoresis allows for the transdermal delivery of charged drugs under the influence of a low-level electric current. Recently iontophoretic technology has been used to deliver lidocaine to provide rapid, noninvasive local anesthesia. Studies have also demonstrated the ability to obtain systemic opiate levels using this technology. In this article we review the history and principles of iontophoresis as well as the literature supporting its use for both local anesthesia and systemic analgesia.

Dexamethasone↗