The influence of emulsifiers on drug diffusion from o/w creams

Histamine diffusion from various o/w creams containing different emulsifiers was studied. To confirm the diffusion study, possible drug-emulsifier interactions were studied by dialysis of their aqueous solutions. Interaction between histamine and anionic sodium laurylsulphate resulted in the absence of free diffusible histamine. No interaction was observed with the non-ionic cetomacrogol. Repulsion by the cationic cetrimide increased histamine diffusion rate and total diffusing amount because distribution occurred in accordance with the Donnan membrane equilibrium.     

New strategies to improve skin barrier homeostasis

The uppermost thin layer, stratum corneum, plays a crucial role as a water impermeable barrier. After acute damage, it recovers automatically, but with aging or psychological stress, the recovery is delayed. Frequent damage, or damage under a dry environment, induces epidermal hyperplasia or inflammation. A specific protease inhibitor, histamine antagonist, and some magnesium salts have been demonstrated to accelerate the barrier recovery. These treatments also mitigated the epidermal hyperplasia induced by repeated barrier disruption or the damage under a dry condition. For the delay of the barrier repair induced by psychological stress, a glucocorticoid receptor antagonist or reduction of the stress by some specific odorant was significantly effective. Recently, the ion flux in the epidermis was found to be crucial for the barrier homeostasis. An external negative electric field accelerated the skin barrier recovery. These new methods to improve skin barrier homeostasis could be useful strategies to solve skin problems.     

Quantification of human skin barrier function and susceptibility to quantum dot skin penetration

Abstract In this study, we utilize in vivo human skin and a viable ex-vivo human skin model to investigate the effect of a commercial depilatory agent on barrier function. Tape stripping was used as a positive control. The magnitude of skin barrier was quantified by measuring transepidermal water loss values on in vivo human skin and transepithelial electrical resistance measurements and tissue histology on ex vivo skin. The susceptibility to carboxylated quantum dot penetration through ex vivo skin was investigated using fluorescent microcopy analysis of microtomed skin sections and flow cytometry to quantify quantum dot association with live epidermal cells. Results show that depilatory treatment modifies the outside-in barrier sufficiently to allow quantum dots to penetrate the stratum corneum but to a lesser extent than tape stripping. The implications of these finding are discussed.     

Quantification of human skin barrier function and susceptibility to quantum dot skin penetration

Abstract

In this study, we utilize in vivo human skin and a viable ex-vivo human skin model to investigate the effect of a commercial depilatory agent on barrier function. Tape stripping was used as a positive control. The magnitude of skin barrier was quantified by measuring transepidermal water loss values on in vivo human skin and transepithelial electrical resistance measurements and tissue histology on ex vivo skin. The susceptibility to carboxylated quantum dot penetration through ex vivo skin was investigated using fluorescent microcopy analysis of microtomed skin sections and flow cytometry to quantify quantum dot association with live epidermal cells. Results show that depilatory treatment modifies the outside-in barrier sufficiently to allow quantum dots to penetrate the stratum corneum but to a lesser extent than tape stripping. The implications of these finding are discussed.     

Miconazole,a pharmacological barrier to skin fungal infections

Introduction: Miconazole (MCZ) is a time-honored antifungal of the imidazole class. MCZ exerts a multipronged effect on fungi. It inhibits the cytochrome P450 complex, including the 14α-demethylase enzyme required for ergosterol biosynthesis, in fungal cell membranes. In addition, intracellular accumulation of toxic methylated sterols occurs and the synthesis of triglycerides and phospholipids is altered. Disturbances in oxidative and peroxidative enzyme activities lead to an intracellular toxic concentration of hydrogen peroxide. As a result, intracellular organelle destruction then leads to cell necrosis. Farnesol synthesis stimulated in Candida spp. prevents the yeast-to-mycelium formation. MCZ is further active against Gram-positive bacteria.

Areas covered: This review aims at revisiting the MCZ antifungal activity in dermatomycoses.

Expert opinion: MCZ's wide spectrum of activity appears noteworthy. The full pharmacological profile of MCZ indicates its fungistatic profile through its effect on ergosterol biosynthesis. In addition, it exhibits a fungicidal effect against a number of fungal species, due to hydrogen peroxide accumulation. MCZ is characterized by high safety, efficacy and versatility, and a unique, multifaceted nature of activity in the treatment of dermatomycoses.     

Miconazole, a pharmacological barrier to skin fungal infections

INTRODUCTION: Miconazole (MCZ) is a time-honored antifungal of the imidazole class. MCZ exerts a multipronged effect on fungi. It inhibits the cytochrome P450 complex, including the 14α-demethylase enzyme required for ergosterol biosynthesis, in fungal cell membranes. In addition, intracellular accumulation of toxic methylated sterols occurs and the synthesis of triglycerides and phospholipids is altered. Disturbances in oxidative and peroxidative enzyme activities lead to an intracellular toxic concentration of hydrogen peroxide. As a result, intracellular organelle destruction then leads to cell necrosis. Farnesol synthesis stimulated in Candida spp. prevents the yeast-to-mycelium formation. MCZ is further active against Gram-positive bacteria. AREAS COVERED: This review aims at revisiting the MCZ antifungal activity in dermatomycoses. EXPERT OPINION: MCZ's wide spectrum of activity appears noteworthy. The full pharmacological profile of MCZ indicates its fungistatic profile through its effect on ergosterol biosynthesis. In addition, it exhibits a fungicidal effect against a number of fungal species, due to hydrogen peroxide accumulation. MCZ is characterized by high safety, efficacy and versatility, and a unique, multifaceted nature of activity in the treatment of dermatomycoses.     

Penetration of theophylline and adenosine into excised human skin from binary and ternary vehicles: effect of a nonionic surfactant

A nonionic surfactant, diethyleneglycol lauryl ether (PEG-2-L), increases the flux of either theophylline or adenosine by a factor of 2.2-2.7, when these are delivered from propionic acid solutions into human skin samples, with respect to propionic acid alone. At the same time, the flux of propionic acid from the same vehicles is decreased. Significant expansion of the partial molal volumes vi of both purines occurs following incorporation of PEG-2-L into their propionic acid solution. Hence, the enhancing effect of this surfactant arises mainly from an increase in the excess free energy of these solutes in the donor phase ("push" effect). Paraffin oil increases the flux of either drug from propionic acid by an entirely different mechanism. It enhances the flux of propionic acid into the skin, thus promoting the partitioning of the purine solute in the modified skin barrier ("pull" effect). Indeed, the magnitude of vi of either purine in propionic acid:paraffin oil solution gives no indication of a significant interaction between paraffin oil and the purine solute. Finally, the penetration enhancing effects of PEG-2-L and paraffin oil combined together in the same propionic acid vehicle are additive, resulting in a flux which is approximately the sum total of fluxes obtained separately with PEG-2-L or paraffin oil.     

Evaluation of anionic surfactants effects on the skin barrier function based on skin permeability

Anionic surfactants are often used for cleaning and pharmaceutical purposes because of their strong surfactancy and foaming property. However, they are rarely ingested orally, the skin is a part of the human body most affected by surfactants. Barrier function of the skin is very strong, but the anionic surfactants can cause serious damages to it. Recently, amino acid-based surfactants have attracted attention as a safer option owing to their biocompatibility. Cytotoxicity examinations revealed that the amino acid-based surfactants are superior to sulfate-based surfactants. However, a systematical and comprehensive study related to the effect of these surfactants on skin barrier function has not yet been reported. In this work, skin permeation test using the skin of hairless mice and HPLC method is carried out. The material transmission speed through skin in a steady state was different between each surfactant treatment. We performed a comprehensive analysis of the effect of surfactants on skin barrier function and defined Transmission Index as an index for the degree of effect of surfactants. Glutamate series amino acid-based surfactant were effective to Transmission Index and we guessed the cause was due to adsorption. Based on the finding this study, we suggest using adsorptive property as a measure to the effect on the skin barrier function.     

Release of salicylic acid, diclofenac acid and diclofenac acid salts from isotropic and anisotropic nonionic surfactant systems across rat skin

Release of salicylic acid, diclofenac acid, diclofenac diethylamine and diclofenac sodium, from lyotropic structured systems, namely; neat and middle liquid crystalline phases, across mid-dorsal hairless rat skin into aqueous buffer were studied. Release results were compared with those from the isotropic systems. The donor systems composed of the surfactant polyoxyethylene (20) isohexadecyl ether, HCl buffer of pH 1 or distilled water and the specific drug. High performance liquid chromatography (HPLC) methods were used to monitor the transfer of the drugs across the skin barrier. Results indicated that the rate-determining step in the transport process was the release of the drug from the specified donor system. Further, apparent zero order release was demonstrated with all systems. Except for diclofenac sodium, drug fluxes decreased as the donor medium changed from isotropic to anisotropic. The decrease in fluxes was probably due to the added constrains on the movement of drug molecules. By changing the anisotropic donor medium from neat to middle phase, drug flux decreased in case of salicylic acid and diclofenac sodium. In the mean time, flux increased in case of the diethylamine salt and appeared nearly similar in case of diclofenac acid. Rates of drug transfer across the skin from the anisotropic donors seemed to be largely controlled by the entropy contribution to the transport process. The type and extent of drug-liquid crystal interactions probably influenced the latter.     

Using skin models to assess the effects of a protection cream on skin barrier function

BACKGROUND: There is a basic necessity to understand the mechanisms of the protective effects of emulsions. This would promote the development of protective cosmetics and therefore improve the prevention and treatment of occupational skin diseases. However, for such studies, no reliable skin model is available. OBJECTIVE: An in vitro skin model test was developed to evaluate the protective mechanism of cosmetic ingredients. METHODS: The efficacy of three products was assessed by an in vivo test (Repetitive Occlusive Irritation Test) and then 3-dimensional skin model tests were carried out. RESULTS: In vivo test results demonstrate that the best protection against sodium dodecyl sulphate is offered by a multiple emulsion. In the case of a skin model test, sodium dodecyl sulphate led to cell damage, an increase in pro-inflammatory markers and some barrier lipids. The multiple emulsion increased the content of skin lipids, without inducing irritation or cell death. CONCLUSION: Skin models react similarly to sodium dodecyl sulphate compared to human skin and therefore they are suitable to study barrier repair after sodium dodecyl sulphate damage. It is likely that the superior protective effect of the multiple emulsion in vivo is based on the increased amount of skin barrier lipids.     

An insight into the role of barrier related skin proteins

It is well-known that intercellular lipids in the stratum corneum (SC) of the skin play an important role in maintaining barrier function, and many types of penetration enhancers affecting lipids are used in topical products to improve transdermal drug permeability. Recently, it was reported that functional proteins in tight junctions of the epidermis are important for barrier function. In this study, the effects of penetration enhancers such as fatty esters, amines/amides, and alcohols on the barrier function of the skin were evaluated in rat skin and normal human-derived epidermal keratinocytes (NHEK). All penetration enhancers decreased the electrical impedance (EI), however, the potencies of some penetration enhancers were not equal between rat skin and NHEK. The differences were clarified by immunohistochemical studies: some fatty esters decreased the immunoreactivity of involucrin and keratin 10 in the upper layer of the epidermis, while alcohols decreased the immunoreactivity of desmoglein-1, claudin-1, and E-cadherin located in the lower layer of the epidermis. From these results, it is suggested that penetration enhancers show new action mechanisms disturbing barrier-related proteins in epidermis, which are classified into two categories depending on their action sites.     

Topical application of ionic polymers affects skin permeability barrier homeostasis

We previously demonstrated that the external electric potential affected skin barrier homeostasis. On the other hand, topical application of an ionic polymer formed a diffusion electric double layer on the surface of the skin. Thus, we evaluated effects of topical application of ionic polymers on the damaged skin barrier. Application of a nonionic polymer did not affect barrier recovery. Application of sodium salts of anionic polymers accelerated barrier recovery, while that of cationic polymers delayed it. Topical application of a sodium-exchange resin accelerated barrier recovery, but application of a calcium-exchange resin had no effect even when the resins had the same structure. Application of a chloride-exchange resin delayed barrier recovery. Topical application of ionic polymers influenced skin barrier homeostasis.     

Evaluation of penetration enhancement of lidocaine by nonionic surfactants through hairless mouse skin in vitro

The effect of two nonionic surfactants (polyoxyethylene sorbitan monoesters) on percutaneous absorption of lidocaine in the presence of various concentrations of propylene glycol is reported. Comparisons were made in vitro using excised hairless mouse skin as the barrier membrane. Under infinite dose conditions, steady-state flux was enhanced by surfactants at high propylene glycol concentrations. The same trend was observed following application of a thin layer of formulation to the skin (finite-dose conditions). However, penetration behavior was complex due to: (a) changes in vehicle composition following application, (b) temperature changes resulting from evaporation or moisture uptake, and (c) depletion of lidocaine as a result of penetration with compositions that lost water by evaporation. Two peaks in the flux versus time curve were observed. Surfactant monomer concentration in the vehicles was increased in the presence of propylene glycol.     

In vivo percutaneous absorption,skin barrier perturbation,and irritation from JP-8 jet fuel components

JP-8 jet fuel has been reported to cause systemic and dermal toxicities in animal models and humans. There is a great potential for human exposure to JP-8. In this study, we determined percutaneous absorption and dermal toxicity of three components of JP-8 (i.e., xylene, heptane, and hexadecane) in vivo in weanling pigs. In vivo percutaneous absorption results suggest a greater absorption of hexadecane (0.43%) than xylene (0.17%) or heptane (0.14%) of the applied dose after 30 min exposure. Transepidermal water loss (TEWL) provides a robust method for assessing damage to the stratum corneum. Heptane showed greater increase in TEWL than the other two chemicals. No significant (p < 0.05) increase in temperature was observed at the chemically treated site than the control site. Heptane showed greater TEWL values and erythema score than other two chemicals (xylene and hexadecane). We did not observe any skin reactions or edema from these chemicals. Erythema was completely resolved after 24 h of the patch removal in case of xylene and hexadecane.