Combination Of Iontophoresis Research Articles

Effect of permeation enhancers on the iontophoretic transport of metoprolol tartrate and the drug retention in skin

Utilization of chemical penetration enhancers in conjunction with iontophoresis is regarded as the most effective method to enhance the passage of molecules across the skin barrier. A systematic approach to enhance the transdermal delivery of metoprolol tartrate and the subsequent release of the drug depot in the skin was investigated. Gel formulations with proximate viscosity were prepared and assessed for the effect of polymers (carbopol, hydroxypropyl methyl cellulose, and methyl cellulose), permeation enhancers (5%w/w, sodium lauryl sulfate (SLS), dimethyl formamide, n-methyl-2-pyrrolidone, and polyethylene glycol 400), and the combination approach (permeation enhancers with iontophoresis–0.5 mA/cm2) on the drug delivery. The flux values observed in passive (4.59–5.89 µg/cm2/h) and iontophoresis (37.99–41.57 µg/cm2/h) processes revealed that the permeation of metoprolol was not influenced by the polymers studied, under similar conditions, and further studies were carried out using carbopol gel as a representative polymer. Appreciable enhancement (∼ 5-fold) in drug delivery was observed with SLS in the passive process while the optimum iontophoretic delivery condition ensured better delivery (∼ 7-fold). Combination of iontophoresis with SLS further enhanced the drug delivery (∼ 9-fold) and leads to noticeable drug retention in the skin as well. Moreover, the drug retained in the cutaneous layer of the skin eventually released over a period of time (5 days) and followed a near first order profile. This study concludes that the combination of iontophoresis with SLS augmented the metoprolol delivery and rendered skin drug depot, which eventually released over a period of time.

Electrically assisted delivery of macromolecules into the corneal epithelium

Electrically assisted delivery is noninvasive and has been investigated in a number of ocular drug delivery studies. The objectives of this study were to examine the feasibility of electrically assisted delivery of macromolecules such as small interfering RNA (siRNA) into the corneal epithelium, to optimize the iontophoresis and electroporation methods, and to study the mechanisms of corneal iontophoresis for macromolecules. Anodal and cathodal iontophoresis, electroporation and their combinations were the methods examined with mice in vivo. Cyanine 3 (Cy3)-labeled glyceraldehyde-3-phosphate dehydrogenase (GAPDH) siRNA and fluorescein isothiocyanate (FITC)-labeled dextran of different molecular weights (4–70 kDa) were the macromolecules studied. Microscopy and histology after cryostat sectioning were used to analyze and compare the delivery of the macromolecules to the cornea. Iontophoresis was effective in delivering siRNA and dextran up to 70 kDa into the cornea. The electroporation method studied was less effective than that of iontophoresis. Although both iontophoresis and electroporation alone can deliver the macromolecules into the cornea, these methods alone were not as effective as the combination of iontophoresis and electroporation (iontophoresis followed by electroporation). The significant enhancement of dextran delivery in anodal iontophoresis suggests that electroosmosis can be a significant flux-enhancing mechanism during corneal iontophoresis. These results illustrate the feasibility of electrically assisted delivery of macromolecules such as siRNA into the cornea.

Electric field assisted transdermal drug delivery from salicylic acid-loaded polyacrylamide hydrogels

The apparent diffusion coefficients, Dapp, and the release mechanisms of salicylic acid from polyacrylamide hydrogels through pigskin were investigated. Dapp increases with increasing electric field strength and reaches the maximum value at electric field strength of 0.1 V; beyond that it decreases with increasing electric field strength and becomes saturated at 5 V. The increase in Dapp at low electric field strength can be attributed to the combination of iontophoresis, electroporation of matrix pore, and induced pathway in pigskin. Dapp obeys the scaling behavior Dapp/Do = (drug size/pore size)m with m equal to 0.67 and 0.49 at the electric field strengths of 0 and 0.1 V, respectively.

Delivery of a classical antihypertensive agent through the skin by chemical enhancers and iontophoresis

Oral therapy with antihypertensive agents is generally associated with severe GI side effects and low patient compliance. Therefore, development of a method of drug delivery that maintains the proper drug level for a prolonged period without adverse effects is required. Thus, transdermal delivery has all the necessities that are required for delivery of classical antihypertensive agents. However, the different approaches to enhance the transport of atenolol through intact skin have not resulted in a remarkable improvement. The effect of the drug concentration and a binary system (water-ethanol) on the atenolol flux was investigated. Further, the effects of chemical enhancers (menthol, oleic acid, polyethylene glycol 400, sodium lauryl sulphate, di methyl formamide and N-methyl-2-pyrrolidone) at different concentrations and their combined effects with iontophoresis were examined. Among the binary systems, the highest flux was obtained when 75% v/v ethanol in water was used. Atenolol flux enhanced significantly (P<0.001) at the 5% w/v concentration among all the enhancers studied. It was also observed that the combination of iontophoresis with oleic acid (5% w/v) showed the maximum benefit with a steady-state flux of 2.66 mumol/cm(2)/h. The combination of iontophoresis with permeation enhancers was found to be promising in delivering atenolol across the skin, and the highest permeation was attained when oleic acid was combined with iontophoresis. The in vitro flux value obtained (when oleic acid combined with iontophoresis) was 0.71 mg/cm(2)/h, which points to the fact that a therapeutically effective concentration can be attained with 1.2 cm(2) of skin contact area.

Enhancement of skin permeation of high molecular compounds by a combination of microneedle pretreatment and iontophoresis

A combination of microneedle pretreatment and iontophoresis was evaluated for the potential to increase skin permeation of drugs. Two model compounds with low and high molecular D 2O and fluorescein isothiocyanate (FITC)-dextrans (FD-4, FD-10, FD-40, FD-70 and FD-2000; average molecular weight of 3.8, 10.1, 39.0, 71.2 and 200.0 kDa), respectively, were used and the effect of microneedle pretreatment and iontophoresis on their in vitro permeability was evaluated using excised hairless rat skin with a 2-chamber diffusion cell. Convective solvent flow through the skin was measured using a set of calibrated capillaries attached to the diffusion cell. The following results were obtained: (1) convective solvent flow (electroosmosis) during iontophoresis through microneedle-pretreated skin, 2.62 ± 0.32 μL/cm 2/h, was almost the same as through intact skin, 2.71 ± 0.25 μL/cm 2/h, and (2) the combination of microneedle pretreatment and subsequent iontophoresis significantly enhanced FD flux compared with microneedle pretreatment alone or iontophoresis alone, whereas no synergistic effect was found on the flux of D 2O. These results suggest that the combination of iontophoresis with microneedle pretreatment may be a useful means to increase skin permeation of high molecular compounds.

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.

Cutaneous side-effects of transdermal iontophoresis with and without surfactant pretreatment: a single-blinded, randomized controlled trial

Iontophoresis, a method that facilitates drug transport across skin by an external electrical field, offers the possibility for long-term transdermal delivery of compounds in a well-controlled manner. In general, the literature supports the contention that iontophoresis is a safe procedure. However, there are important medical issues concerning the epidermal and dermal effects of iontophoresis that have not been extensively investigated. Specific and strictly controlled studies on the dermal effect of iontophoresis are scarce. The aim of this study was to investigate the cutaneous side-effects of transdermal iontophoresis application in healthy human volunteers. This was a single-blinded, randomized and parallel design study. In one group (n=12) subjects were treated nonocclusively with a surfactant formulation followed by iontophoresis (3-h application at a current density of 250 microA cm(-2)). In another group (n=12) iontophoresis alone was performed. No drug was included in these studies. The corresponding passive treatments served as controls. Noninvasive methods including sensation record, transepidermal water loss (TEWL), skin colour and the visual scoring were used to assess cutaneous effects. Tingling and itching were commonly experienced in the first 30 min of the current application. Iontophoresis in combination with the pretreatment induced significant increases in TEWL values and in skin redness, and resulted in slight to mild erythema and oedema compared with the control. Compared with the iontophoresis alone, the presence of surfactant pretreatment caused slightly more skin irritation (erythema and oedema) but did not further disturb the skin barrier function. The transdermal iontophoresis challenges the skin barrier function and induces transient mild skin irritation, but does not cause any permanent damage to the skin when applied for 3 h at a current density of 0.25 mA cm(-2).

Effect of Chemical Penetration Enhancer and Iontophoresis on the In Vitro Percutaneous Absorption Enhancement of Insulin Through Porcine Epidermis

The purpose of this study was to investigate the effect of chemical enhancers (fatty acids and limonene) and iontophoresis on the in vitro permeability enhancement of insulin through porcine epidermis. The following fatty acids were used: palmitic (C16:0), palmitoleic (C16:1), stearic (C18:0), oleic (C18:1), linoleic (C18:2), and linolenic (C18:3). Franz diffusion cells and the Scepter™ iontophoretic power source were used for the percutaneous absorption studies. Cathodal iontophoresis was performed at 0.2 mA/cm2 current density. Iontophoresis in combination with chemical enhancers synergistically increased (p < 0.05) the in vitro permeability of insulin. Linolenic acid (C18:3) produced greater permeability of insulin through epidermis than did other fatty acids during passive (44.45 × 10− 4 cm/h) and iontophoretic (78.03 × 10− 4 cm/h) transport. Lispro insulin flux was significantly (p < 0.05) greater through linolenic acid and limonene pretreated epidermis compared to untreated controls during both passive and iontophoretic transports. Using limonene as a penetration enhancer, a linear increase in the passive and iontophoretic flux of lispro insulin was observed with donor concentrations increasing from 100 IU/mL to 300 IU/mL. Iontophoretic flux through limonene-treated epidermis using 0.5 mA/cm2 current density and 300 IU/mL insulin donor solution was 45.63 IU/cm2/day. Using an iontophoretic patch size of 10 cm2, we would be able to deliver 50 IU of insulin within 3 h.

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 ( X 1), electroporation ( X 2) and stripped skin ( X 3) 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.

Iontophoretic Enhancement of Leuprolide Acetate by Fatty Acids, Limonene, and Depilatory Lotions Through Porcine Epidermis

The effect of chemical enhancers (e.g., fatty acids, limonene, depilatory lotions) and iontophoresis was investigated on the in vitro permeability of leuprolide acetate through porcine epidermis. Franz diffusion cells and Scepter™ iontophoretic power source were used for the percutaneous absorption studies. Anodal iontophoresis was performed at 0.2 mA/cm2 current density. Fatty acids used were palmitic (C16:0), palmitoleic (C16:1), stearic (C18:0), oleic (C18:1), linoleic (C18:2), and linolenic (C18:3) acids. The passive and iontophoretic flux were significantly (p < 0.05) greater through fatty acids‐treated porcine epidermis in comparison to the control (untreated epidermis) for leuprolide acetate. The passive and iontophoretic permeability of leuprolide acetate increased with increasing number of cis double bonds. Among the fatty acids tested, linolenic acid (C18:3) exhibited the maximum permeability of leuprolide acetate during passive (51.42 × 10− 4 cm/hr) and iontophoretic (318.98 × 10− 4 cm/hr) transport. The passive and iontophoretic flux of leuprolide acetate were significantly (p < 0.05) greater through the limonene and depilatory lotion treated epidermis in comparison to their respective control. In conclusion, iontophoresis in combination with chemical enhancers synergistically increased (p < 0.05) the in vitro permeability of leuprolide acetate through porcine epidermis.

Transdermal delivery of timolol and atenolol using electroporation and iontophoresis in combination: a mechanistic approach.

The purpose of this work was to study the effect of electroporation on iontophoretic transport of two beta-blockers, timolol (lipophilic) and atenolol (hydrophilic), and to have a better understanding of the mechanism of combination. The transdermal delivery of these beta-blockers through human stratum corneum was studied in three-compartment diffusion cells. The transport of mannitol was evaluated to assess the electroosmotic flow. The iontophoretic transport of timolol was decreased by electroporation because the high accumulation of the lipophilic cation timolol in the stratum corneum resulted in a decrease of electroosmosis. In contrast, electroosmosis was not affected by atenolol, and the iontophoretic transport of atenolol was increased by electroporation. Using two different beta-blockers, we showed that lipophilicity and positive charges affect the electrotransport of drugs. Understanding the effect of the physicochemical properties of the drug, as well as the electrical parameters, is thus essential for the optimization of transdermal drug delivery by a combination of electroporation and iontophoresis.

Electronically facilitated transdermal delivery of human parathyroid hormone (1–34)

Electronically facilitated transdermal delivery of human parathyroid hormone (1–34), hPTH (1–34), was investigated in vitro, using dermatomed porcine skin. The effect of iontophoretic current density, electroporative pulse voltages and also electroporation followed by iontophoresis was investigated on the in vitro percutaneous absorption of hPTH (1–34). Iontophoresis at 0.5 mA/cm 2 current density significantly enhanced ( P<0.05) the flux of hPTH (1–34) in comparison to passive flux. Electroporation pulses of 100, 200 and 300 V significantly increased ( P<0.05) the flux of hPTH (1–34) in comparison with the passive as well as iontophoretic flux at 0.5 mA/cm 2. The electroporative flux of hPTH (1–34) was found to vary linearly ( R 2=0.97) with the pulse amplitude. The principal barrier of the skin, stratum corneum, was found perturbed following the pulses as evident by light microscopy studies. The application of electroporation pulses followed by iontophoresis further increased the flux by several fold. The flux of hPTH (1–34) with the electroporation pulses of 100 and 300 V followed by iontophoresis at 0.2 mA/cm 2 was 10- and 5-fold higher, respectively, in comparison to the flux with corresponding pulses alone. This shows the synergistic effect of iontophoresis in combination with electroporation on skin permeability of hPTH (1–34). The results indicate the possibility of designing controlled transdermal delivery systems for hPTH (1–34) using electroporation followed by iontophoresis.

Transdermal delivery of diclofenac sodium gel after iontophoresis

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

Transdermal iontophoresis of sodium nonivamide acetate: V. Combined effect of physical enhancement methods

The effect of iontophoresis combined with treatment of other physical enhancement methods such as electroporation, low frequency ultrasound, and erbium:YAG (yttrium–aluminum–garnet) laser on the transdermal delivery of sodium nonivamide acetate (SNA) was examined in this present study. Iontophoresis increased the transdermal flux of SNA in vitro as compared to the passive diffusion without any enhancement. Furthermore, iontophoresis was always the most potent enhancement method for SNA permeation among the physical enhancement methods tested. Pulsing of high voltages (electroporation) followed by iontophoresis did not result in increased transport over iontophoresis alone. However, electroporation shortened the onset of transdermal iontophoretic delivery of SNA. Pretreatment of low frequency ultrasound (sonophoresis) alone on skin did not increase the skin permeation of SNA. The combination of iontophoresis and sonophoresis increased transdermal SNA transport more than each method by itself. The enhancement of drug transport across shunt routes and reduction of the threshold voltage in the presence of an electric field may contribute to this synergistic effect. Use of an erbium:YAG laser was a good method for enhancing transdermal absorption of SNA because it allows precise control of stratum corneum (SC) removal, and this ablation of SC could be reversible to the original normal status. The combination of laser treatment and iontophoresis also synergized the skin permeation of SNA, possibly due to a gradual drop in the electric resistance of the skin. The results in this present study point out that the choice of certain conditions with suitable physical enhancement methods can induce a synergistic effect on transdermal delivery of SNA during iontophoresis.

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 μg/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.

Passive and iontophoretic delivery of three diclofenac salts across various skin types.

The in vitro permeation of three diclofenac salts--diclofenac sodium (DFS), diclofenac potassium (DFP) and diclofenac diethylammonium (DFD)-across skin by both passive and iontophoretic transport were investigated. Various skin types were used as the barriers to elucidate the mechanism controlling transdermal delivery of diclofenac salts. The importance of the intercellular (paracellular) route for both DFS and DFP in passive permeation was elucidated. The transfollicular route constitutes an important permeation pathway for DFS but not for DFP. The route and mechanism for transdermal iontophoresis of DFD across the skin was somewhat different to that of the other salts. Hair follicles may be a more important pathway for DFD than for DFS and DFP under iontophoresis, while the intercellular lipid pathway showed the opposite result. Combination of iontophoresis and a penetration enhancer, cardamom oil, did not show a synergistic effect on diclofenac salt permeation. The results of this investigation suggest that the transdermal mechanism and the route of diclofenac salt uptake via passive and iontophoretic transport can be affected by their counterions.

Effect of linolenic acid/ethanol or limonene/ethanol and iontophoresis on the in vitro percutaneous absorption of LHRH and ultrastructure of human epidermis

The effect of enhancer(s) (e.g. ethanol (EtOH), 5% linolenic acid/EtOH, and 5% limonene/EtOH) and iontophoresis was investigated on the in vitro percutaneous absorption of luteinizing hormone releasing hormone (LHRH) and ultrastructure of human epidermis by transmission electron microscopy (TEM). 5% linolenic acid/EtOH or 5% limonene/EtOH significantly enhanced ( P<0.05) the passive flux of LHRH through human epidermis in comparison to the control (no enhancer treated epidermis). Iontophoresis further increased the flux of LHRH through enhancer(s) treated epidermis. Iontophoretic flux of LHRH through 5% linolenic acid/EtOH and 5% limonene/EtOH treated epidermis was significantly ( P<0.05) enhanced in comparison to iontophoretic flux through the control epidermis. TEM is the most efficient way to visualize the ultrastructure of the stratum corneum (SC). TEM results reveal that iontophoresis in combination with enhancers (e.g. linolenic acid/EtOH or and limonene/EtOH) transformed the highly compact cells of the SC into a looser network of filaments, disrupted the keratin pattern, and resulted in swelling of SC cell layers of human epidermis. Thus, linolenic acid/EtOH or limonene/EtOH in combination with iontophoresis increased the flux of LHRH through human epidermis by disrupting keratin pattern as well as loosening and swelling of SC cell layers.

Synaptically evoked dendritic action potentials in rat neocortical pyramidal neurons.

In a previous study iontophoresis of glutamate on the apical dendrite of layer 5 pyramidal neurons from rat neocortex was used to identify sites at which dendritic depolarization evoked small, prolonged Ca2+ spikes and/or low-threshold Na+ spikes recorded by an intracellular microelectrode in the soma. These spikes were identified as originating in the dendrite. Here we evoke similar dendritic responses by electrical stimulation of presynaptic elements near the tip of the iontophoretic electrode with the use of a second extracellular electrode. In 9 of 12 recorded cells, electrically evoked excitatory postsynaptic potentials (EPSPs) above a minimum size triggered all-or-none postsynaptic responses similar to those evoked by dendritic glutamate iontophoresis at the same site. Both the synaptically evoked and the iontophoretically evoked depolarizations were abolished reversibly by blockade of glutamate receptors. In all recorded cells, the combination of iontophoresis and an EPSP, each of which was subthreshold for the dendritic spike when given alone, evoked a dendritic spike similar to that evoked by a sufficiently large iontophoresis. In one cell tested, dendritic spikes could be evoked by the summation of two independent subthreshold EPSPs evoked by stimulation at two different locations. We conclude that the dendritic spikes are not unique to the use of glutamate iontophoresis because similar spikes can be evoked by EPSPs. We discuss the implications of these results for synaptic integration and for the interpretation of recorded synaptic potentials.

Effect of penetration enhancers and iontophoresis on the FT-IR spectroscopy and LHRH permeability through porcine skin

The present study explores the effect of enhancer and iontophoresis on the in vitro permeability of luteinizing hormone releasing hormone (LHRH) through porcine epidermis and biophysical changes in the stratum corneum lipids by Fourier transform infrared (FT-IR) spectroscopy. Enhancers (e.g. ethanol, 10% oleic acid in combination with ethanol and 10% oleic acid in combination with propylene glycol) pretreatment increased ( P<0.05) the permeability coefficient of LHRH. Propylene glycol alone did not increase the permeability ( P>0.05) of LHRH through the epidermis. Iontophoresis further increased the permeability of LHRH ( P<0.05) through the enhancers (ethanol, 10% oleic acid in combination with ethanol, propylene glycol and 10% oleic acid in combination with propylene glycol) pretreated epidermis in comparison to the control (without enhancer pretreated epidermis). This shows that iontophoresis can synergize with enhancers, such as 10% oleic acid in combination with ethanol and 10% oleic acid in combination with propylene glycol, to provide an additional driving force to maintain and control the target flux of LHRH. The FT-IR spectroscopic study was performed to investigate the effect of the above enhancers and iontophoresis on the biophysical changes in the stratum corneum lipids. Pretreatment of the stratum corneum with 10% oleic acid in combination with ethanol, and 10% oleic acid in combination with propylene glycol followed by iontophoresis shifted the antisymmetric peak position with reference to the control (without enhancer and iontophoresis) from 2919.3±0.7 to 2927.6±4.1, and 2919.3±0.7 to 2924.2±1.9 cm −1, respectively. Thus, the combination of enhancer and iontophoresis increased the average acyl chain disorder (lipid fluidity). The synergism in enhancement of the permeability of LHRH through the epidermis by iontophoresis in combination with enhancers (10% oleic acid in combination with ethanol, and 10% oleic acid in combination with propylene glycol) may be due to greater fluidization of the stratum corneum lipids.

Effect of iontophoresis in combination with ionic enhancers on the lipid structure of the stratum corneum: an X-ray diffraction study.

Effect of iontophoresis in combination with ionic enhancers on the lipid structure of the stratum corneum: an X-ray diffraction study.