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PubMed2002

Effect of permeation enhancer pretreatment on the iontophoresis of luteinizing hormone releasing hormone (LHRH) through human epidermal membrane (HEM).

A 2 x 2 factorial design was performed to determine the effect of a permeation enhancer (oleic acid/propylene glycol), iontophoresis (2 V), and the combination of the two treatments on the permeation enhancement of a model peptide, LHRH (luteinizing hormone releasing hormone), through human epidermal membrane (HEM). In parallel studies, TEAB (tetraethylammonium bromide, a small ionic solute) and sucrose (an electroosmotic flow marker) were also investigated. Structural changes in the HEM were monitored via conductance measurements, differential scanning calorimetry (DSC), and infrared (IR) spectroscopy experiments. LHRH enhancement due to enhancer in combination with iontophoresis (I + E; 29.5 times passive permeability, P), was greater than during iontophoresis alone (I; 14.3) and enhancer treatment alone (E; 3.5). I + E had an additive effect of I and E, indicating the mechanisms of action of the individual enhancement strategies were likely to be located at different sites in the skin. Also, no synergistic enhancement was observed with I + E for either TEAB or sucrose. For TEAB, permeability enhancement due to I (approximately 1400) was much higher than that due to E (14.9), and no additive effect could be detected. For sucrose, E had no effect on either passive or iontophoretic permeability, eliminating the possibility that electroosmosis could explain increases in LHRH permeability. Evidence of synergy between E and I was found, with conductance measurements indicating that I + E synergistically increased the membrane permeability to conducting ions (Na+ and Cl-). It appears these pathways were not available for transport for the solutes used in the current study. DSC and IR investigations showed significant changes in stratum corneum lipid structure following E treatment but not following I. These findings probably arise from the localized action of iontophoresis compared with the bulk action of enhancer. In summary, increased LHRH delivery through HEM in vitro can be achieved using an enhancer in combination with iontophoresis.

Calorimetry, Differential Scanning↗

PubMed2001

Quantification of pore induction in human epidermal membrane during iontophoresis: the importance of background electrolyte selection.

It has been shown that significant pore induction (electroporation) occurs in human epidermal membrane (HEM) during iontophoresis even at moderate applied voltages (1-10 V). Recent efforts in our laboratory have been aimed at quantifying HEM electroporation by examining the proportionality between flux enhancement due to electroporation and electrical conductance changes during iontophoresis. The specific purpose of the present study was to test the hypothesis that by matching the background electrolyte ion sizes with the permeant ion sizes, the flux enhancement due to electroporation can be quantified by the change in HEM electrical conductance. In this study, radiolabeled tetraethylammonium (TEA(+)), methylammonium (MA(+)), and mannitol were the permeants. Potassium chloride (KCl), tetraethylammonium bromide (TEAB), tetraethylammonium pivalate (TEAP), and sodium fluoride (NaF) were the background electrolytes. Iontophoresis experiments were carried out over an applied voltage range of 1 to 3 V. The experimental flux enhancement results were compared with the theoretical predictions from the Nernst-Planck model after corrections were made: (a) for HEM pore induction during iontophoresis based on electrical conductance changes and (b) for electroosmosis employing mannitol as the neutral probe permeant. In experiments where the ion sizes of the background electrolyte and permeant were closely matched (e.g., TEA(+) as the permeant and TEAP as the background electrolyte), there was excellent agreement between experimental results and theoretical predictions of the modified Nernst-Planck model, with only modest data scatter. When the electrolyte and permeant sizes were quite different (e.g., TEA(+)/KCl and MA(+)/TEAP), the experimental flux data were inconsistent with model predictions and there were large variations in the experimental results. The results of the present study illustrate that permeant flux enhancement can be predicted by the modified Nernst-Planck model even during moderate voltage iontophoresis when electroporation is operative.

Electric Impedance↗

PubMed1998

[Therapy of hyperhidrosis with tap water iontophoresis. Positive effect on healing time and lack of recurrence in hand-foot eczema].

Hyperhidrosis is due to an overfunction of eccrine glands (triggered by the autonomous nervous system) and may be a cofactor for palmoplantar eczema (dermatitis). Tapwater iontophoresis was used in 54 patients with hyperhidrosis manuum et pedum. After 10 applications directed by the dermatologist, 89% of patients noted an improvement in their hyperhidrosis. 20 patients suffering from palmoplantar eczema (dermatitis) who continued the treatment at home for at least 6 months were compared with a historical sex- and age-matched group of 20 eczema-patients without iontophoresis: The factors evaluated were the time needed for clearing and the relapse-free interval. Though iontophoresis-treated patients had a slightly faster clearing, this was statistically not significant (20 vs. 22.3 days; p > 0.05). However, the difference for relapse-free interval between the two groups was statistically highly significant (24.8 weeks vs. 8.35 weeks; p < 0.0001). Tapwater iontophoresis seems to be effective not only to control sweating. According to recently published data, galvanization seems to have a capsaicin-like effect as well. Our hypothesis is therefore, that galvanization with tapwater iontophoresis interrupts the neurogenic inflammation and prolongs the relapse-free interval in hyperhidrotic palmoplantar eczema (dermatitis).

Adult↗

PubMed2003

Reverse iontophoresis: a non-invasive technique for measuring blood urea level.

Monitoring of the urea level of patients with insufficient kidney function requires repetitive blood sampling. The potentially painful nature of blood sampling and the difficulty of venous access, particularly in premature neonates, as well as possible complications of needle injuries, create many disadvantages. A non-invasive technique needs to be developed for monitoring the urea level for these patients. Reverse iontophoresis has recently gained importance and the possibility of extracting some compounds from body fluids using reverse iontophoresis has been reported in the literature. Moreover, a small, watch-type device has been developed for the determination of blood glucose levels using a similar approach. The aim of the current study was to investigate the possibility of extracting urea from blood through skin using reverse iontophoresis to monitor blood urea levels without taking a blood sample. In vitro iontophoresis studies have indicated that urea may be successfully transferred through the full thickness of human skin. The reverse iontophoresis technique was applied to 17 patients with kidney insufficiency and urea was successfully extracted through their skin into the collection solution. A high correlation ( r(2)=0.878) between urea concentrations in collection solutions and urea levels in the blood was observed. These results suggest that it is possible to make a watch-type device for monitoring blood urea levels.

Adult↗

PubMed2006

Transdermal delivery of heparin using pulsed current iontophoresis.

PURPOSE: In clinical practice heparin has to be administered by injection with obvious disadvantages; thus, transdermal delivery by electrically assisted methods have been studied. In this study we evaluated the efficacy of a Food and Drug Administration-approved pulsed current iontophoresis system in delivering heparin through living rat skin. METHODS: Fluorescent and radioactive heparin as well as a commercial heparin preparation were delivered through rat skin via a pulsed current iontophoresis system. RESULTS: Pulsed current iontophoresis allowed fluorescent heparin to cross the stratum corneum localizing in epidermis and dermis. Unfractionated, high-, and low molecular weight fraction pools, obtained by fractionating [35S]-unfractionated heparin on a molecular weight sieve, were then separately tested. Pulsed current iontophoresis elicited the transdermal delivery of low molecular weight heparin, but not that of high molecular weight heparin. Finally, pulsed current iontophoresis of an unfractionated pharmaceutical heparin preparation significantly decreased plasmatic factor Xa activity. CONCLUSIONS: We hypothesize that this technique could be used to administer low molecular weight heparin in a cost-efficient and safe manner without the need for syringes and needles.

Administration, Cutaneous↗

PubMed2006

Topical iontophoresis of valaciclovir hydrochloride improves cutaneous aciclovir delivery.

PURPOSE: To investigate the topical iontophoresis of valaciclovir (VCV) as a means to improve cutaneous aciclovir (ACV) delivery. METHODS: ACV and VCV electrotransport experiments were conducted using excised porcine skin in vitro. RESULTS: While the charged nature of the prodrug, VCV, enabled it to be more efficiently iontophoresed into the skin than the parent molecule, ACV, only the latter was detectable in the receptor chamber, suggesting that VCV was enzymatically cleaved into the active metabolite during skin transit. Iontophoresis of VCV was significantly more efficient than that of ACV; the cumulative permeation of ACV after 1, 2 and 3 h of VCV iontophoresis at 0.5 mA cm(-2) and using an aqueous 2 mM (approximately 0.06%) formulation was 20+/-10, 104+/-47 and 194+/- 82 microg cm( -2), respectively (cf. non-quantifiable levels, 0.1 and 1.0+/-0.7 microg cm(-2) after ACV iontophoresis). CONCLUSIONS: These delivery rates provide ample room to reduce either current density or the duration of current application. Preliminary in vitro data serve to emphasize the potential of VCV iontophoresis to improve the topical therapy of cutaneous herpes simplex infections and merit further investigation to demonstrate clinical efficacy.

Acyclovir↗

PubMed1995

Lidocaine via iontophoresis in laceration repair: a preliminary safety study.

Iontophoresis is a painless technique for topical anesthesia that uses an electric field to drive charged ions across an epithelial surface. The safety of this technique for laceration repair has never been demonstrated. The purpose of this study was to investigate the effect of iontophoretic fields on rapidly proliferating cells involved in laceration wound healing. The study was a prospective single-blinded animal study using a guinea pig model. Twelve guinea pigs each received four induced, uncontaminated lacerations. Each guinea pig was randomly assigned to 1 of 3 groups (4 guinea pigs in each group). One group received lidocaine via iontophoresis, one group received injected lidocaine, and one group received half iontophoresis and half injected lidocaine. After anesthetic treatment, wounds were then repaired in a standard fashion. The wounds were examined grossly on a daily basis and on day 10 the incised skin containing the laceration was examined by a pathologist blinded to the treatment group. A total of 48 wounds were assessed for wound healing, 24 of which received lidocaine via iontophoresis and 24 lidocaine via injection. The power of the study to determine a 40% difference between the two groups was 0.8. There was significantly more granuloma and granulation tissue formation in the iontophoresis group than in the injected lidocaine control group (P = .0004, Fisher's exact test).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2004

Skin vasoreactivity to insulin iontophoresis is reduced in elderly subjects and is absent in treated non-insulin-dependent diabetes patients.

We investigated the skin vasoreactivity to insulin in normal subjects and in treated non-insulin-dependent diabetes mellitus (NIDDM) patients. We measured cutaneous perfusion by laser-Doppler flowmetry (LDF) at rest and during skin cathodal iontophoresis (six pulses of 0.1 mA each for 20 s, with 40 s interval between stimulations) of insulin (0.1 ml Humulin R 100 IU/ml diluted 1/10 with of 0.9% saline solution) in 45 healthy subjects (HS), (25 males, 20 females, aged 45 +/- 18 years), and in 15 treated NIDDM patients (13 males), aged 66 +/- 8 years. Fifteen of the HS were used as controls. In these 15 sex- and age-matched HS and in the patients, we assessed also the skin postischemic hyperemia by LDF. In HS cutaneous blood flux response (CBF) to iontophoresis of insulin in saline (expressed as percent changes from baseline) was significantly higher than CBF response to iontophoresis of pure saline (maximum response: 360 +/- 51% versus 172 +/- 42%, respectively; P < 0.001, ANOVA for repeated measures). The maximum "net" CBF response to insulin (response to insulin minus response to saline) showed a negative correlation (r = -0.361; P < 0.01) with age in HS, and resulted significantly lower in the oldest than in the youngest HS (105 +/- 40% versus 307 +/- 45%, respectively; P < 0.01). No significant correlation was observed between the maximum CBF response to saline and the age of subjects. In NIDDM patients the "net" CBF response to insulin iontophoresis resulted significantly lower than in 15 sex- and age-matched control subjects (maximum response: -50 +/- 89% versus 201 +/- 81%, respectively; P < 0.001, ANOVA for repeated measures). No significant difference was observed between diabetics and controls, nor in basal perfusion (6.5 +/- 1.3 IU versus 6.8 +/- 1.7 IU, respectively) neither in the skin postischemic hyperemia (250 +/-14% versus 258 +/- 27%, respectively). These results confirm that insulin iontophoresis induces a skin vasodilatatory effect in normal subjects and show that this effect is reduced by aging and is absent in treated NIDDM patients. The local skin vasodilatatory effect induced by insulin seems to involve mechanisms different from those underlying the skin postischemic hyperemia.

Adult↗

PubMed2004

Mechanistic studies of flux variability of neutral and ionic permeants during constant current dc iontophoresis with human epidermal membrane.

Although constant current iontophoresis is supposed to provide constant transdermal transport, significant flux variability and/or time-dependent flux drifts are observed during iontophoresis with human skin in vitro and human studies in vivo. The objectives of the present study were to determine (a) the causes of flux variability in constant current dc transdermal iontophoresis and (b) the relationships of flux variabilities among permeants of different physicochemical properties. Changes in the human epidermal membrane (HEM) effective pore size and/or electroosmosis during constant current dc iontophoresis were examined. Tetraethylammonium ion (TEA), urea, and mannitol were the model permeants. For the neutral permeants, the results in the present study showed a significant increase of fluxes with time in a given experiment and large HEM sample-to-sample variability. Although both effective pore size and pore charge density variations contributed to the time-dependent flux drifts observed in electroosmotic transport, the significant flux drifts observed were found to be primarily a result of the time-dependent increase in effective pore charge density. For the ionic permeant, the observed flux variability was smaller than that of the neutral permeants and was believed to be primarily due to effective pore size alteration in HEM during iontophoresis as suggested in a previous study. The different extents of flux variability observed between neutral and ionic permeants are consistent with the different iontophoretically enhanced transport mechanisms for the neutral and ionic permeants (i.e. electroosmosis and electrophoresis, respectively). The results of the present study also demonstrate that flux variability of two neutral permeants are inter-related, so the flux of one neutral permeant can be predicted if the permeability coefficient of the other neutral permeant is known.

Biological Transport↗

PubMed2005

Transcorneal and transscleral iontophoresis of dexamethasone phosphate using drug loaded hydrogel.

PURPOSE: To evaluate dexamethasone penetration to the eye after a short transcorneal and transscleral iontophoresis using a drug loaded hydrogel assembled on a portable iontophoretic device. METHODS: Iontophoresis of dexamethasone phosphate was studied in healthy rabbits using drug loaded disposable HEMA hydrogel sponges and portable iontophoretic device. Corneal iontophoretic administration was performed with a current intensity of 1 mA for 1 and 4 min. Transconjunctival and transscleral iontophoresis were performed twice for 2 min at two near places in the pars-plana area, on the conjunctival membrane or directly on the sclera. Dexamethasone concentrations were assayed using HPLC. RESULTS: Dexamethasone levels in the rabbit cornea after a single transcorneal iontophoresis for 1 min were up to 30 fold higher compared to those obtained after frequent eye drop instillation. Also, high drug concentrations were obtained in the retina and sclera 4 h after transscleral iontophoresis. CONCLUSIONS: A short low current non-invasive iontophoretic treatment using dexamethasone-loaded hydrogels has potential clinical value in increasing drug penetration to the anterior and posterior segments of the eye.

Animals↗

PubMed2004

Role of histamine release in nonspecific vasodilatation during anodal and cathodal iontophoresis.

Nonspecific vasodilatation during iontophoresis is an important confounding factor in experimental pharmacology. In this investigation, we studied the involvement of sensory nerves and histamine-related reactions in causing nonspecific vasodilatation in a model of anodal and cathodal iontophoresis of sodium chloride. Firstly, we applied a mixture of local anesthetic (EMLA) cream to confirm its suppressive effect on nonspecific vasodilatation and to measure its efficacy in three different dosages (duration: 1, 2, and 3 h). We then investigated the role of histamine in nonspecific vasodilatation by giving an oral antihistamine drug (cetirizine) to subjects who had and had not been given EMLA. We found substantial suppression of the nonspecific vasodilatation in all EMLA-treated groups (all dosages) compared with untreated controls (with suppression rates of 60-65%). Dosage had no significant effect. A further suppression of nonspecific vasodilatation was seen after oral cetirizine during anodal and cathodal iontophoresis in both EMLA-treated and untreated groups. The antihistamine effect was most pronounced during anodal iontophoresis. These results suggest a histaminergic increase in perfusion that may be independent of neurogenic mechanisms and depend on polarity (anode or cathode). Local nerve blocks (EMLA) together with cetirizine may therefore be used to reduce nonspecific vasodilatation in both anodal and cathodal iontophoresis.

Administration, Oral↗

PubMed1999

Iontophoresis: a needle-free, electrical system of local anesthesia delivery for pediatric surgical office procedures.

BACKGROUND/PURPOSE: Delivery of local anesthesia for surgical office procedures for pediatric patients can be difficult. Injections are painful and often lead to patient anxiety, and topical anesthetics frequently provide incomplete anesthesia. The authors prospectively studied the efficacy of iontophoresis, a needle-free technique in which positively charged lidocaine and epinephrine molecules are drawn into the tissue by an electrical current as an anesthetic for pediatric surgical office procedures. METHODS: Children undergoing an office procedure were offered local anesthesia via iontophoresis. Prospectively collected data included patient characteristics, procedure, iontophoresis dose and time, need for additional injected anesthetic, pain during the procedure as determined by a 0 to 5 faces scale, and complications. A satisfaction questionnaire was completed at the follow-up visit or by telephone. RESULTS: Over an 8-month period, 34 patients with a mean age of 6.8 years (range, 3 months to 15 years) underwent 38 office procedures with anesthesia supplied through iontophoresis. Skin lesion excision (n = 14) and abscess drainage (n = 12) were the most common procedures. Seven patients required unplanned injected anesthetic. A small, superficial burn was the only complication. Sixty percent of patients and 84% of parents rated pain as 0 to 2 (zero to mild). Overall, 88% were satisfied with the anesthetic. CONCLUSION: Iontophoresis appears to be an effective and safe alternative method of local anesthesia delivery for pediatric surgical office procedures.

Ambulatory Surgical Procedures↗

PubMed1991

Device drug delivery to the eye. Collagen shields, iontophoresis, and pumps.

External devices have been used to enhance drug delivery. This article reviews the role of collagen shields, iontophoresis, and pumps used to deliver ophthalmic medications. Collagen shields have been used to deliver drugs and promote corneal epithelial healing. Presoaked collagen shields deliver many drugs to the eye as well as or better than traditional methods such as frequent topical therapy or subconjunctival injection. The efficacy of drug delivery by collagen shields was demonstrated in animal models of graft rejection and bacterial keratitis. Iontophoresis uses an electrical current to carry an ionized drug across tissue. Transcorneal iontophoresis delivers high concentrations of a drug to the anterior segment of the eye. Transscleral iontophoresis bypasses the lens-iris diaphragm and produces adequate vitreous levels. Pumps deliver fluid to the eye for extended periods of time via a tube with its distal opening in the conjunctival sac, corneal stroma, anterior chamber, or vitreous cavity. Clinical acceptance of the collagen shield for drug delivery to the anterior segment is better than iontophoresis or pumps, probably because the collagen shield is simpler and more convenient to use.

Absorption↗

PubMed2000

Effect of saline iontophoresis on skin barrier function and cutaneous irritation in four ethnic groups.

The effect of saline iontophoresis on skin barrier function and irritation was investigated in four ethnic groups (Caucasians, Hispanics, Blacks and Asians). Forty healthy human volunteers were recruited according to specific entry criteria. Ten subjects, five males and five females, were assigned to each ethnic group. Skin barrier function was examined after 4 hours of saline iontophoresis at a current density of 0.2 mA/cm(2) on a 6.5 cm(2) area in terms of the measured responses: transepidermal water loss (TEWL), skin capacitance, skin temperature and visual scores. There were significant differences in TEWL among the ethnic groups prior to patch application. TEWL at baseline in ethnic groups was in the rank order: Caucasian>Asian>Hispanic>Black. Iontophoresis was generally well tolerated, and skin barrier function was not irreversibly affected by iontophoresis in any group. There was no significant skin temperature change, compared to baseline, in any ethnic groups at any observation point. Edema was not observed. At patch removal, the erythema score was elevated in comparison to baseline in all ethnic groups; erythema resolved within 24 hours. Thus, saline iontophoresis produced reversible changes in skin barrier function and irritation in healthy human subjects.

Adolescent↗

PubMed2003

Post-iontophoresis transport of ibuprofen lysine across rabbit ear skin.

The aim of this work was to study in vitro the post-iontophoresis transport of ibuprofen lysine across rabbit ear skin, from ibuprofen lysine water solutions (20-200 mg/ml and pH 6.8-7.8). Current densities of 0.125, 0.25, and 0.5 mA/cm(2) were applied either continuously or for 15, 30, and 60 min followed by passive diffusion for up to 5h. The results showed a significantly higher cathodal transport compared to passive flux. Anodal iontophoresis also increased ibuprofen permeation, even though the drug is negatively charged. The application of an electric current for a limited period of time, followed by passive diffusion from the reservoir in contact with the skin, produced much higher post-iontophoresis fluxes of ibuprofen than passive diffusion. Post-iontophoresis transport of ibuprofen from lysine salt solutions linearly depended on the total amount of current applied during iontophoresis, and in the absence of background ions was independent of donor drug concentration. The reason for this behavior was the creation of a drug reservoir in the skin owing to the short period of current application.

Animals↗

PubMed1999

Evaluation of transdermal iontophoresis of enoxacin from polymer formulations: in vitro skin permeation and in vivo microdialysis using Wistar rat as an animal model.

Polymers were used in vehicles to form hydrogel matrices in this study to evaluate the in vitro permeation and in vivo microdialysis of enoxacin. The highest transdermal delivery determined by area under flux-time curve (AUC) and intracutaneous enoxacin concentration were observed in methylcellulose (MC) and polyvinylpyrrolidone (PVP) hydrogels, respectively. To avoid the pH shift in vehicles during iontophoresis, buffer species were added to formulations to increase the buffer capacity. As expected, the permeability of enoxacin of anodal iontophoresis was larger than that of cathodal iontophoresis. Combination of benzalkonium chloride, a cationic surfactant as an enhancer, and iontophoresis exerted an enhancing effect for anionic enoxacin at pH 10.0. However, no effect or a negative effect was detected for cationic enoxacin in deionized water or pH 5.0 buffer, due to the shielding of the negative charge in the skin. The skin residue of enoxacin was slightly increased after the incorporation of Azone in PVP hydrogel. The result of in vivo microdialysis was in accordance with that of in vitro study. The effect of Azone on the intracutaneous enoxacin was more significant for in vivo microdialysis than in the in vitro study indicating the clinical feasibility of Azone for iontophoretic delivery. Microdialysis can be considered as a useful technique to investigate the pharmacokinetics of transdermal iontophoresis in vivo.

Administration, Cutaneous↗

PubMed2003

Effect of iontophoresis and fatty acids on permeation of arginine vasopressin through rat skin.

The aim of this study was to assess the effects of fatty acids and iontophoretic mode of penetration enhancement on transdermal delivery of Arginine Vasopressin (AVP). Sprague-Dawley (SD) rat skin was pretreated with fatty acids (e.g. 5% w/v, lauric acid, oleic acid, and linoleic acid in ethanol:water (EtOH:W, 2:1 system) for 2h and iontophoresis in vitro, separately or together. The results indicate that all fatty acids studied increased (P<0.05) the flux of AVP in comparison to control (not pretreated with enhancer) and their effectiveness in flux enhancement was comparable. Further, oleic acid in combination with iontophoresis significantly increased the permeation of AVP both in comparison to pretreatment with fatty acids and iontophoresis alone. However, iontophoresis did not further increase the permeation of AVP through linoleic acid pretreated skin. Fourier transform infrared (FT-IR) spectroscopic studies revealed that EtOH:W (2:1) system is not effective in lipid extraction. The shift to higher wavenumbers of the symmetric and asymmetric stretching peaks at 2850 and 2920cm(-1) revealed that at the concentration used, oleic acid and linoleic acid caused fluidization of stratum corneum (SC) lipids. This study provides direct evidence that oleic acid in EtOH:W (2:1) system causes disruption of the SC lipid lamellae and that a combination of oleic acid with iontophoresis further enhances the effects of oleic acid in a synergistic manner.

Administration, Cutaneous↗

PubMed1997

Effect of penetration enhancers and iontophoresis on the ultrastructure and cholecystokinin-8 permeability through porcine skin.

The present study explores the effect of chemical penetration enhancers and iontophoresis on the in vitro permeability of cholecystokinin-8 (CCK-8) through porcine epidermis and on the ultrastructural changes in stratum corneum as observed by transmission electron microscopy (TEM). Enhancer [i.e., ethanol (EtOH), and 10% oleic acid in combination with ethanol (OA/EtOH)] pretreatment significantly increased (p < 0.01) the permeability coefficient of CCK-8 in comparison with the control (pretreated epidermis without enhancer). Iontophoresis further increased the permeability of CCK-8 (p < 0.01) through the enhancer-pretreated epidermis in comparison with the control. These results showed the synergistic effect of iontophoresis and enhancers such as OA/EtOH that provides an additional driving force to maintain and control the target flux of CCK-8. The ultrastructure of stratum corneum treated with ethanol demonstrated a loss of structural components in the superficial stratum corneum cell layers. OA/EtOH transformed the highly compact cells of stratum corneum into a looser network of filaments, creating an increased free volume and greater intracellular surface area. Treatment of stratum corneum with OA/EtOH followed by iontophoresis resulted in further swelling of stratum corneum cell layers. In conclusion, OA/EtOH in combination with iontophoresis increased the permeability of CCK-8 by loosening and swelling of stratum corneum cell layers.

Animals↗