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At least 127 records · Page 7Linked to original sources

PubMed1995

Iontophoresis enhances the transport of acyclovir through nude mouse skin by electrorepulsion and electroosmosis.

PURPOSE: Iontophoresis was employed for enhancing the transdermal delivery of acyclovir through nude mouse skin in vitro, with the aim of understanding the mechanisms responsible for drug transport, in order to properly set the conditions of therapeutical application. METHODS: Experiments were done in horizontal diffusion cells, using as donor a saturated solution of acyclovir at two different pH values (3.0 and 7.4). Different electrical conditions (current density and polarity) were employed. RESULTS: At pH 3.0, acyclovir anodal transport was due to electrorepulsion, since acyclovir was 20% in the protonated form. In acyclovir anodal iontophoresis at pH 7.4 the main mechanism involved was electroosmosis, since the drug was substantially unionized and the negative charge of the skin at this pH caused the electroosmotic flow to be from anode to cathode. In the case of cathodal iontophoresis at pH 3.0, acyclovir transport was enhanced approx. seven times, due to the presence of an electroosmotic contribution caused by the reversal of the charge of the skin. At pH 7.4 during cathodal iontophoresis acyclovir transport was not enhanced because the electroosmotic flow was in the opposite direction, compared to drug electric transport, i.e. anode to cathode. The increased skin permeability caused by current application was demonstrated to be less important than electrorepulsion and electroosmosis. CONCLUSIONS: Anodal iontophoresis shows potential applicability for enhancing acyclovir transport to the skin, considering that both electric transport and electroosmosis can be used by appropriately setting the pH of the donor.

Acyclovir↗

PubMed1993

Convective solvent flow across the skin during iontophoresis.

Enhanced flux of neutral solutes during transdermal iontophoresis is attributed largely to electroosmotic volume flow. In this study, the iontophoretic fluxes of tritiated water (3H2O) and 14C-labeled mannitol through hairless mouse skin (HMS) were determined. The following questions were addressed: (i) What is the variability of water flux during iontophoresis? (ii) To what extent is the iontophoretic flux of a neutral solute correlated with water flux? (iii) Does the intrinsic permeability of the skin to neutral solutes change following iontophoresis? (iv) What is the effect of low pH on electroosmotic volume flow? and (v) Does the skin remain permselective after removal of the stratum corneum? Transport of both water and mannitol reached steady-state levels during 10 hr of constant-current iontophoresis (0.36 mA/cm2). Anodal fluxes exceeded cathodal values. Cathodal mannitol flux was retarded, relative to passive transport, by net volume flow in the opposite direction, such that transport of this molecule increased significantly after the termination of current passage. Anodal equivalent volume flows for water and mannitol, respectively, were 2.7 (+/- 1.3) and 1.23 (+/- 0.59) microL/hr cm2, indicating that only approximately 50% of the water flux participated in the electroosmosis of mannitol. The passive permeability of water and mannitol after 10 hr of iontophoresis was, respectively, 6 and 30 times greater than the pretreatment values. At pH 7, the cationic permselectivity of HMS was marginal [the Na+ transport number (tNa+) was determined to be 0.46] and less than that reported for human skin.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗

PubMed2004

Reverse iontophoresis as a noninvasive tool for lithium monitoring and pharmacokinetic profiling.

PURPOSE: Transdermal iontophoresis was investigated as a noninvasive tool for drug monitoring and pharmacokinetic profiling. Lithium, a frequently monitored drug, was used as a model. The objectives were a) to demonstrate the linear dependence of the iontophoretic extraction flux of lithium on the subdermal concentration of the drug, b) to evaluate the capacity of iontophoresis to monitor sudden changes in the subdermal level, c) to investigate the utility of reverse iontophoresis as a tool in pharmacokinetic studies, and d) to examine the validity of an internal standard calibration procedure to render the method completely noninvasive. METHODS: Transdermal, iontophoretic extraction was performed in vitro using dermatomed pig-ear skin. The subdermal solution consisted of a physiological buffer containing lithium chloride at concentrations in the therapeutic range and two putative internal standards, sodium and potassium, at fixed physiological levels. The subdermal concentration of lithium was changed either in a stepwise fashion or by simulating one of two pharmacokinetic profiles. RESULTS: Lithium was extracted via electromigration to the cathode. A excellent correlation between subdermal lithium concentration and iontophoretic extraction flux was observed. Iontophoresis tracked sudden concentration changes and followed kinetic profiles. In addition, the effective elimination rate constant could be directly, and noninvasively, estimated from the extraction flux data. CONCLUSIONS: Reverse iontophoresis is a potentially useful and noninvasive tool for lithium monitoring.

Administration, Cutaneous↗

PubMed2000

Structural and functional effects of oleic acid and iontophoresis on hairless mouse stratum corneum.

The aim of this study was to assess the effects of chemical and electrical modes of percutaneous penetration enhancement on the intercellular lipid lamellae of the stratum corneum. Hairless mice were treated with either oleic acid/propylene glycol and iontophoresis separately or together. Permeability barrier function was evaluated by measuring transepidermal water loss and correlated with the structure of stratum corneum intercellular lamellae, as evaluated by electron microscopy, using ruthenium tetroxide postfixation. Transepidermal water loss levels did not change following 1 h iontophoresis alone. In contrast, topical applications of 0.3 M oleic acid in propylene glycol for 1 h increased transepidermal water loss significantly. Moreover, the combined use of iontophoresis plus 0.3 M oleic acid for 1 h further increased transepidermal water loss at equivalent time points. Ultrastructural observations demonstrated both marked disorganization of the intercellular lipid lamellae, as well as the presence of distended lacunae within the stratum corneum in oleic acid/propylene glycol plus or minus iontophoresis-treated stratum corneum. This study provides direct evidence that the oleic acid/propylene glycol system can disrupt the stratum corneum lipid lamellar structures, and that coapplications of oleic acid with iontophoresis further enhance the effects of oleic acid. The synergy between chemical and physical enhancement may afford a new approach to promote transdermal drug delivery.

Animals↗

PubMed2003

Iontophoresis and sonophoresis stimulate epidermal cytokine expression at energies that do not provoke a barrier abnormality: lamellar body secretion and cytokine expression are linked to altered epidermal calcium levels.

We performed this study to identify whether the expression of epidermal cytokines is altered by changes in epidermal calcium content, independent of skin barrier disruption. Iontophoresis and sonophoresis with the energies that do not disrupt the skin barrier, but induce changes in the epidermal calcium gradient, were applied to the skin of hairless mice. Immediately after iontophoresis and sonophoresis, immersion in a solution containing calcium was carried out, and iontophoresis in either high- or low-calcium solutions was performed. The biopsy specimens were taken for real-time quantitative RT-PCR to detect changes in mRNA level of interleukin-1alpha (IL-1alpha), tumor necrosis factor-alpha (TNF-alpha), and transforming growth factor-beta in the epidermis and for immunohistochemical stain with primary antibodies to IL-1alpha and TNF-alpha. The expression of each cytokine mRNA increased in the epidermis treated with iontophoresis and sonophoresis compared to a nontreated control as well as in tape-stripped skin used as a positive control and was lower after immersion in a high-calcium solution than in low-calcium solution. IL-1alpha and TNF-alpha immunohistochemical protein staining increased with iontophoresis at low calcium. These studies suggest that changes in epidermal calcium can directly signal expression of epidermal cytokines in vivo, independent of changes in barrier function.

Animals↗

PubMed2003

Iontophoresis with or without dexamethazone in the treatment of acute Achilles tendon pain.

The purpose of this double-blind study was to evaluate the effects of iontophoresis with dexamethazone to iontophoresis with saline solution on patients who had acute (less than 3 months) pain from the Achilles tendon, in terms of range of motion, muscular endurance, pain and symptoms. Twenty-five patients (15 men and 10 women), aged between 18 and 76 years (mean=38), were evaluated before and after 2 weeks of treatment with iontophoresis, as well as after 6 weeks, 3 and 6 months and 1 year. Two groups were treated for 2 weeks with iontophoresis for each treatment. Three ml of dexamethazone were used for the experiment group (n=14) and 3 ml of saline solution for the control group (n=11). Both groups then followed the same rehabilitation programme for 10 weeks. Good reliability was found for the toe-raise and range of motion tests. Poor reliability was, however, found for the pain on palpation test, which was therefore excluded. No difference was found between or within groups for the toe-raise test. Several significant improvements were seen in the experiment group but not in the control group, in the range of motion test, pain during and after physical activity, pain during walking and walking up and down stairs, morning stiffness and tendon swelling. Even though the small sample size limits the possibilities to draw definite conclusions, we conclude from the present study, using a double-blind, randomised approach and a 1-year follow-up period, that positive effects from using iontophoresis with dexamethazone were found in the treatment of patients with acute Achilles tendon pain.

Achilles Tendon↗

PubMed2001

Etofenamate levels in human serum and synovial fluid following iontophoresis.

The absorption of etofenamate (CAS 30544-47-9, Rheumon gel) by iontophoresis in 11 patients with low back pain and in 13 patients with synovitis of the knee was evaluated. During the 5-day treatment period, the test gel in a quantity corresponding to 100 mg etofenamate was applied to affected body regions every day by 20-min iontophoresis sessions. Two hours after the fifth application, the concentration of etofenamate in serum and synovial fluid (in patients who had knee joint iontophoresis) were measured by HPLC. Iontophoresis of etofenamate into the lumbar region as well as to the knee joint resulted in consistent serum levels: 219 +/- 136.3 micrograms/l and 191 +/- 84.6 micrograms/l, respectively. In patients with synovitis of the knee, the synovial level of etofenamate (368 +/- 109.2 micrograms/l) was almost twice as high than the serum concentration. The authors conclude that with topical application of etofenamate by iontophoresis the drug appears not only in the serum but also--with higher levels--in the synovial fluid.

Administration, Topical↗

PubMed2000

Effect of sodium dodecyl sulfate on iontophoresis of hydrocortisone across hairless mouse skin.

The purpose of the present work was to study the effect of sodium dodecyl sulfate (SDS), an anionic surfactant, on the iontophoretic transport of a neutral drug hydrocortisone (HC) across hairless mouse skin. The transport studies were conducted using Side-Bi-Side diffusion apparatus and drug concentration in the receptor cell was analyzed using reversed-phase HPLC. A theoretical model was described, tested, and found to agree well with experimental data (R2 = 0.9766). Anodal iontophoresis significantly enhanced the transport of HC compared to cathodal iontophoresis and passive diffusion, suggesting that the transport of the neutral solute occurs via the electro-osmotic flow. The effect of SDS on the transport of HC was highly concentration-dependent and driving mode-dependent. Below the critical micelle concentration (cmc), increasing the concentration of SDS increased both the passive and the iontophoretic fluxes of HC, but the increase was most significant with anodal iontophoresis. Above the cmc, passive transport of HC continued to increase with an increase in the SDS concentration. The transport after anodal iontophoresis, however, reached a plateau and then leveled off. Further increase in SDS concentration decreased flux, suggesting that the transport of micellar-solubilized drug is retarded by anodal iontophoresis, possibly due to electrostatic attraction.

Animals↗

PubMed1999

The distribution of gentamicin in the rabbit cornea following iontophoresis to the central cornea.

The purpose of this study was to evaluate the penetration of gentamicin into the central, midperipheral and peripheral cornea of rabbits following iontophoresis to the central 3 mm of the cornea. Four groups (groups 1-4) of five rabbits (one eye per rabbit) underwent corneal iontophoresis using gentamicin dissolved in agar. Low (1 mg/ml) and high (10 mg/ml) concentrations of gentamicin in agar were used for one or ten minutes. Two control groups (groups 5 and 6) of five eyes each underwent mock iontophoresis with low and high concentrations of agar-gentamicin mixture. Following sacrifice of the rabbits, the central, midperipheral and peripheral parts of each cornea were excised. Gentamicin concentration was determined in each part of every cornea. High concentrations of gentamicin (951.6 +/- 369.4 microg/ml to 26.6 +/- 41.34 microg/ml) were obtained in the central parts of all the iontophoresis-treated corneas. In each group, except group 6, central corneas had higher concentrations of gentamicin compared to midperipheral corneas (p = 0.038 to p = 0.021), and midperipheral corneas had higher levels than peripheral corneas (p = 0.038 to p = 0.021). Following iontophoresis, gentamicin is found in all portions of the corneas; however, the highest concentration of the drug remains in the central cornea.

Analysis of Variance↗

PubMedDate not supplied

The role of gentamicin iontophoresis in the treatment of burned ears.

Ear cartilage heals slowly, and limited vascularity in cartilage precludes use of systemic antibiotics. Iontophoresis electrically induces drugs in solution to migrate into target tissues. Fifteen patients were randomized to receive gentamicin iontophoresis (n = 7) plus dressing changes every 6 hours and cleaning or routine care alone (n = 8) for treatment of ear burns. There were no differences between the groups in incidence of chondritis (43% vs 50%) or cartilage loss (11% vs 16%). However, gentamicin-resistant organisms developed in 29% of the patients who received iontophoresis, but in none of the patients in the control group (p less than 0.05). To identify the etiology of the resistant organisms, 10 New Zealand white rabbits receive 7 cm2 contact burns to each ear. Gentamicin iontophoresis was performed on one ear, and the other ear served as the control. Serum gentamicin levels were always subtherapeutic. Additionally, gentamicin tissue levels in both the treated and control ears were subtherapeutic. Gentamicin iontophoresis appears to offer no additional salutary effects beyond those that are provided by routine care and may encourage the development of antibiotic resistance.

Animals↗

PubMedDate not supplied

Antibiotic iontophoresis in the management of burned ears.

Severe deformities of the ears are a distressing problem after burn injury. Successful management of chondritis has been elusive. Antibiotic iontophoresis has been used in the management of burned ears in patients who have been admitted to the St. Vincent Medical Center Burn Unit since 1983. There were 145 ear burns in 92 consecutive patients who received prophylactic penicillin or gentamicin iontophoresis and who were admitted from 1983 through 1990. A retrospective analysis of all patients who were admitted to the burn unit from 1967 to 1983 was done to review the outcome for patients with burned ears when conventional treatment was used. The incidence of infection, need for chondrectomy, and ear infection were virtually eliminated by management with antibiotic iontophoresis. In addition, no complications were noted when antibiotic iontophoresis was used. Antibiotic iontophoresis provides a safe, simple, and effective way to manage burned ears and thereby limits postburn ear deformities.

Adult↗

PubMed2005

Evaluation of iontophoresis and local corticosteroid injection in the treatment of carpal tunnel syndrome.

OBJECTIVE: The aim of this study was to compare the efficacy of local corticosteroid injection with iontophoresis of corticosteroids in the treatment of carpal tunnel syndrome. DESIGN: This study was a prospective, randomized, unblinded clinical trial with follow-up at 2 and 8 wks. Thirty patients (48 median nerves) with clinical and electrophysiologic evidence of carpal tunnel syndrome were included in the study. Patients were evaluated by use of clinical variables, a functional status scale, a symptom severity scale, and visual analog scale. A total of 48 median nerves were randomly assigned to one of two groups; group 1 received 40 mg of methylprednisolone acetate injected locally in the carpal tunnel, and group 2 received iontophoresis of dexamethasone sodium phosphate. Clinical variables and scales were evaluated at regular intervals: at the beginning and at the end of therapy in the second and eighth week. RESULTS: Twenty-seven patients (90%) were women and three patients (10%) were men. The mean age of patients was 48.0 +/- 8.2 (range, 29-61) yrs. There was a statistically significant improvement in the clinical examination variables, visual analog scale, symptom severity scale, and functional status scale scores of the patients in both of the treatment groups posttreatment (at 2 and 8 wks) compared with baseline (P < 0.05). However, there was a statistically significant difference between the values of the two group. A significant difference in mean symptom severity scale, functional status scale, and visual analog scale scores was found in second week and eighth week in the injection group compared with iontophoresis. CONCLUSION: Our study comparing a standardized treatment protocol for incorporating local corticosteroid injection and iontophoresis of dexamethasone sodium phosphate in carpal tunnel syndrome revealed success of both iontophoresis of dexamethasone sodium phosphate and injection of corticosteroids, but symptom relief was greater at 2 and 8 wks with injection of corticosteroids.

Adult↗

PubMed1992

Iontophoresis of lidocaine for anesthesia during pulsed dye laser treatment of port-wine stains.

Port-wine stains may be effectively ablated using the pulsed dye laser emitting at a wavelength of 577 or 585 nm. However, the discomfort of this therapy may be severe enough to require reduction of treatment duration thereby increasing the need for repeat sessions. Currently available methods of anesthesia or sedation for pulsed dye laser therapy have drawbacks to their use. We performed a prospective double-blind, placebo-controlled evaluation of the iontophoresis of lidocaine HCl 4% and lidocaine HCl 4% with epinephrine 1:50,000 for local anesthesia during pulsed dye laser ablation of port-wine stains. Eleven patients with port-wine stains completed the initial phase of the study. Pain scale evaluation by patients demonstrated significant decreases in the discomfort of pulsed dye laser impulses by the iontophoresis of lidocaine HCl 4% and lidocaine HCl 4% with epinephrine 1:50,000 (P less than .0001), with no significant difference between these treatments. Follow-up evaluation suggests that iontophoresis has no detrimental effect on pulsed dye laser ablation of port-wine stains, despite significant decreases in perfusion, as measured by laser Doppler velocimetry, of port-wine stain areas receiving iontophoresis of lidocaine with epinephrine. Iontophoresis of lidocaine HCl 4% with or without epinephrine is a safe and effective method of local anesthesia for pulsed dye laser therapy.

Adolescent↗

PubMed1997

Reverse iontophoresis: monitoring prostaglandin E2 associated with cutaneous inflammation in vivo.

In response to topical application of irritants, increased concentrations of prostaglandin E2 (PGE2) are found in human skin exudate and in cultured dermal fibroblasts. In this study, PGE2 generated in response to transdermal delivery of irritant drug compounds was monitored in hairless guinea pig (HGP) by a non-invasive method, reverse iontophoresis. Reverse iontophoresis is the movement of molecules from the skin under the influence of an applied electric field. Irritant drug compounds were applied with iontophoresis (electrotransport), and reverse iontophoresis of PGE2 from skin was monitored by radioimmunoassay (RIA) after extraction from the delivery system. Chlorpromazine was used as a model drug irritant. When chlorpromazine and saline were applied over a range of current densities from 0 to 200 microA/cm2, visual scores of erythema and edema yielded a correlation with measured skin efflux of PGE2 (r = 0.86). Delivery of chlorpromazine resulted in greater efflux of PGE2 than delivery of non-irritant saline controls under the same delivery conditions. Five drug compounds, chloroquine, promazine, chlorpromazine, tetracaine, metoclopramide, and saline were applied to hairless guinea pig skin. The 6 agents were similarly rank ordered by visual erythema/edema scores and by PGE2 efflux, indicating that the quantity of PGE2 effluxed reflects the intensity of skin irritation. In contrast, vasoconstriction or vasodilation produced by the local delivery of vasoactive agents did not correlate with PGE2 skin efflux, indicating that this measurement is specific for an inflammatory response. In summary, PGE2 generated in response to transdermally applied drug irritants can be monitored non-invasively in vivo by reverse iontophoresis.

Amebicides↗

PubMed1996

Skin blood flow responses to the iontophoresis of acetylcholine and sodium nitroprusside in man: possible mechanisms.

1. The mechanisms involved in the human skin blood flow responses to iontophoretic application of acetylcholine (ACH; delivered using an anodal charge) or sodium nitroprusside (SNP; administered with a cathodal charge) are unclear. The aims of this study were to investigate possible contributions of prostaglandin production to the increase in skin blood flow induced following the iontophoresis of ACh and to investigate possible contributions from local sensory nerves to the perfusion responses induced by ACh, SNP and their vehicles. 2. The contribution of prostaglandins to the ACh response was determined in a randomized double-blind study of eight healthy subjects, who were studied on two occasions. Basal responses to ACh were measured before the oral administration of 600 mg soluble aspirin in diluted orange juice (1 occasion or orange juice (1 occasion) and again 30 min after the drink. The contribution of local sensory nerve activation to the responses to ACh and ACh vehicle (8 subjects) and to SNP and SNP vehicle (7 subjects) was assessed. EMLA (5%) (a eutectic mixture of lignocaine and prilocaine) and placebo cream were applied to two separate areas on the forearm in a double-blind randomized manner 2 h before drug responses were measured. In all studies the skin microcirculation responses to iontophoretically applied drug vehicle (1 site) and drug (2 sites) were recorded by laser Doppler perfusion imaging. 3. The increase in forearm skin perfusion (P < 0.001) in response to the iontophoresis of ACh minus the response to ACh vehicle was not significantly different following placebo or aspirin administration. The increase in forearm skin red blood cell flux (P < 0.001) in response to the iontophoresis of ACh minus the response to ACh vehicle was not significantly different at the placebo-compared with the EMLA-treated site. THe small increase in perfusion (P < 0.001) in response to the iontophoresis of ACh vehicle was significantly inhibited at the EMLA-compared with the placebo-treated site (P < 0.05). The marked increase in perfusion (P < 0.001) in response to the iontophoresis of SNP vehicle was significantly inhibited at the EMLA-compared with the placebo-treated site (P < 0.01). 4. These data suggest that in healthy volunteers: (1) mechanisms other than prostaglandin production and local sensory nerve activation may be involved in the increase in skin perfusion observed following the iontophoretic application of ACh; and (2) stimulation of local sensory nerves may be responsible for the increase in tissue perfusion observed following the iontophoretic application of either ACh vehicle or SNP vehicle.

Acetylcholine↗

PubMed2003

A randomized, double-blind, placebo-controlled trial of vitamin C iontophoresis in melasma.

BACKGROUND: Vitamin C is known to both inhibit melanin formation and reduce oxidized melanin. However, vitamin C does not easily penetrate the skin. In this study, vitamin C iontophoresis was employed in order to enhance vitamin C penetration. OBJECTIVE: The purpose of this study was to evaluate the efficacy of vitamin C iontophoresis for melasma patients. METHODS: Twenty-nine females with melasma were enrolled. For iontophoresis, a vitamin C solution was applied to one side of the face, while distilled water was applied to the other side as a control. The L (luminance) value was measured by a colorimeter to obtain an objective pigmentation parameter. RESULTS: Twelve weeks after iontophoresis, the colorimeter of the treated site showed a significant decrease in the L value (from 4.60 to 2.78, p = 0.002), compared to that of the control site (from 4.45 to 3.87, p = 0.142). CONCLUSION: Vitamin C iontophoresis may be an effective treatment modality for melasma.

Adult↗

PubMedDate not supplied

Attenuation of axon reflexes to compound 48/80 after repeated iontophoresis of compound 48/80 in skin of the human forearm.

The aim of this study was to determine whether the iontophoretic administration of the mast cell degranulator compound 48/80 influences axon reflex vasodilatation in the skin of the human forearm. In stage 1, compound 48/80 was administered by iontophoresis to a circular site in the forearm of 9 healthy men and 8 healthy women on four occasions spread over 24 h. Two control sites were also prepared by passing the iontophoretic current through 0.9% saline. Large wheals initially developed at the compound 48/80 site in 8 of the males and in 2 of the females, but wheals were minimal in all subjects by the fourth administration. In stage 2, compound 48/80 iontophoresis provoked substantial flaring at the first control site, whereas saline iontophoresis induced only minor flaring at the second control site, indicating that compound 48/80 induced axon reflex vasodilatation. However, prior treatment with compound 48/80 inhibited flaring to compound 48/80 in subjects who initially developed wheals, consistent with mast cell degranulation. In stage 3, flaring after iontophoresis of histamine was investigated at the site of compound 48/80 pretreatment and at the second control site in 12 subjects. Flaring was impaired only slightly in 6 subjects who initially developed wheals to compound 48/80. The persistence of flaring indicates that repeated administrations of compound 48/80 did not abolish neurogenic inflammation. Transcutaneous iontophoresis of compound 48/80 may be an attractive alternative to intradermal injection in studies that aim at clarifying the function of mast cells in healthy and diseased skin.

Adolescent↗

PubMed2004

Delivery of gentamicin to the rabbit eye by drug-loaded hydrogel iontophoresis.

PURPOSE: To assess the corneal iontophoretic delivery of gentamicin by drug-loaded hydrogel probe, and to determine the resultant ocular disposition and elimination of the drug from the cornea and anterior chamber. METHODS: Corneal iontophoresis of gentamicin sulfate was studied in healthy white rabbits by using drug-loaded disposable hydroxyethyl methacrylate (HEMA) hydrogel disk probes and a portable mini-ion device designed in the authors' laboratory. The iontophoretic treatment was performed with a current intensity of 1 mA for 60 seconds only. Three control groups were used: mock iontophoresis (no current) for 60 seconds, topical eye drops of fortified gentamicin (1.4%) every 5 minutes for 1 hour, and subconjunctival injection of 0.25 mL of 40 mg/mL gentamicin solution. The animals in the iontophoretic experimental groups were killed at predetermined time points. The gentamicin concentrations in the cornea and aqueous humor were assayed with a fluorescence polarization immunoassay. Analysis of the gentamicin eye pharmacokinetics was performed with a modeling approach. RESULTS: Peak gentamicin concentrations in the cornea (363.1 +/- 127.3 microg/g) and in the aqueous humor (29.4 +/- 17.4 microg/mL) were reached at 0 and 2 hours after the iontophoretic treatment, respectively. The peak gentamicin concentrations after a single iontophoresis treatment were 12 to 15 times higher than those obtained after gentamicin injection or after topical eye drop instillation, and much higher than in mock iontophoresis. The concentration versus time profile of gentamicin in the cornea and the anterior chamber after iontophoresis was appropriately described by applying a two-compartment pharmacokinetic model. CONCLUSIONS: A short iontophoretic treatment using gentamicin-loaded hydrogels has potential clinical value in increasing drug penetration to the anterior segments of the eye and maintaining therapeutic drug levels in the cornea for more than 8 hours.

Animals↗