Visualization of diffusion pathways across the stratum corneum of native and in-vitro-reconstructed epidermis by confocal laser scanning microscopy.

Confocal laser scanning microscopy is a technique that permits the direct visualization in unfixed material of diffusion pathways and the cellular distribution of fluorescent markers after topical applications. This approach, in which the tissue specimen is optically sectioned, allows the study of changes in distribution pattern of applied compounds depending on the vehicle, time and depth without the interference of chemical alterations induced by most of the current techniques used for such studies. Using this technique the permeability properties of in-vitro-reconstructed epidermis were compared with those of the native counterpart. The epidermis was reconstructed by culturing human adult keratinocytes at the air-liquid interface either on fibroblast-populated collagen or on de-epidermized dermis. A fluorescent probe--Nile red (NR)--was applied in three different vehicles--polyethylene glycol (PEG) with a molecule mass of 400 (Da), propylene glycol (PG) and dimethyl sulphoxide (DMSO)--which perturb the SC barrier function to different extents. When NR was applied in PEG and PG on native epidermis, the amount of NR penetrating into and through the SC was very low, but was markedly increased when NR was applied in DMSO. Unlike native epidermis, the reconstructed epidermis allowed rapid NR penetration after the application in any of the solvents used. Furthermore, NR applied on reconstructed epidermis, was distributed quite homogeneously between the cellular and the intercellular spaces throughout the SC, suggesting that not only intercellular lipid structures but also the properties of the cornified envelopes differed markedly from those found in native epidermis.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of surfactants on penetration across the skin*.

Synopsis Many of the properties of surfactants can be related to their ability to concentrate at phase interfaces, leading to a reduction in interracial tension. In biological systems the effects of surfactants are complex, particularly their effect on cell and other membranes, and this can lead to alterations in permeability characteristics. This is of particular relevance when considering the stratum corneum which has long been recognized as the major barrier to skin permeation. The magnitude of skin barrier function alteration is dependent on surfactant structure, both the hydrophobic alkyl chain and the hydropnilic ethylene oxide chain demonstrating some structure-activity behaviour. In many biological systems, including skin, surfactants with a similar hydrophilic group will show maximum membrane activity if they possess a decyl or dodecyl alkyl chain. It is difficult to rationalise this phenomenon, given that such solution properties as partition coefficients and CMCs do not show maxima or minima at these chain lengths. It may be that the physical parameters and molecular dimensions of the decyl/dodecyl chain provide the optimal ability to intercalate with the lipid bilayer structure. There is little doubt that once the surfactant has intercalated with the lipid bilayers in the lamellar liquid crystals of the stratum corneum, fluidity in the hydrophobic regions is increased. Effectively, this leads to a looser, more permeable structure. The significance of data obtained using commercially available surfactants, however, can be questioned on the grounds of purity. The purpose of this review is to describe some of the methods used to evaluate the effects of surfactants on the skin barrier and to discuss recent attempts to predict surfactant action on the skin using various biological and physical techniques. Résumé La plupart des propriétés des surfactants dépend de leur facilitéà se concentrer aux interfaces, menant ainsi à la réduction de la tension interfaciale. Dans le cas d'un système biologique les effets des surfactants sont complexes, particulièrement leur action sur les cellules et les membranes et ceci mène à l'altération des caractéristiques de la perméabilité. Ce point est très pertinent pour le stratum corneum qui a été longtemps considéré comme la principale barrière à la pénétration cutanée. L'importance de l'altération de cette function barrière est en relation avec la structure du surfactant. L'importance de son altération est liée à la fois à la chaîne alkyle hydrophobe et à la chaîne d'oxyde d'éthylène hydrophile ayant une activité due à sa structure. Dans de nombreux systèmes biologiques, incluant la peau, les surfactants avec une chaîne hydrophile identique montreront une activité maximum sur les membranes si ils comprennent une chaîne alkyle décylique ou dodécylique. Il est difficile de démontrer d'une maniére rationnelle ce phénoméne étant donné que les coefficients de partage de telles solutions et les CMC ne permettent pas de déterminer des longueurs de chaines. II se peut que les paramétres physiques et les dimensions moléculaires des chaines décylique et dodécylique fournissent la capacitt optimale il s'intercaler dans la structure lipidique bicouche. II n'y a pas de doute qu'une fois que le surfactant s'est intercale dans cette bicouche liquide de cristaux lamellaires du stratum corneum, la fluiditt dam les regions hydrophobes est accrue. En effet cela mbne a une structure rellchte plus permtable. La valeur des rtsultats obtenus en utilisant des tensio actifs disponibles sur le march6 peut 6tre remise en question en fonction de leur pureté. Le but de cet article est de commenter quelques méthodes appliqutes pour cvaluer les effets des surfactants sur la barriére cutante et de discuter différents essais récents pour prédire I'action du surfactant sur la peau en utilisant diverses techniques physiques et biologiques.

[Study of hydrogels containing amphotensides]. / Badania niektórych wlasciwosci hydrozelowych podlozy zawierajacych amfotenzydy.

Hydrogels containing different amounts of amphotensides--carboxybetaine and amineoxide--have been obtained. It has been stated that obtained preparations in "in vitro" tests showed higher activity than commercially available ones, and their rheological properties--which can be modified in large range--permit to apply them topically with ease.

[The effect of amphoteric tensides on the pharmaceutic availability of model drugs according to formulation]. / Badanie wplywu amfotenzydów na dostepnosc farmaceutyczna modelowych substancji leczniczych z postaci leku.

Pharmaceutical availability of chloramphenicol from o/w emulsion ointment and salicylic acid from tablets as influenced by the kind and concentration of amphoteric tenside has been investigated. It has been shown that amphoterics investigated variously influenced drug release, what makes possible to obtain the form of drug showing desired rate of release.

[Examination of the properties of amphotensides with potential use as pharmaceuticals]. / Badanie wlasciwosci amfotenzydów o potencjalnych mozliwosciach wykorzystania w przemysle farmaceutycznym.

Basic biological, surface-active and emulsifying properties of manufactured amphotensides in comparison with commercial products have been determined. It has been shown that the compounds investigated should be utilized as auxiliary substances in pharmaceutical technology. There is especially advisable to apply them as emulsifiers for o/w emulsions.

Kinetic analysis of drug release from hydrogels containing amphoteric surfactants.

A one compartment open model was used in order to describe chloramphenicol release from hydrogels containing amphoteric surfactants as gelling agents. Such interpretation seems to be more profitable than that based on Higuchi's root square equation. Using the proposed model it is possible to consider that drug release takes place from the water phase near the surface of membrane, rather than from the micellar phase in which drug seems to be immobilized.

Studies on the release of drugs from O/W emulsion ointments using mathematical interpretations. Part 4: Kinetic analysis of drug release from thick layers.

A kinetic two-compartment model has been used in order to described drug release from thick layers of O/W emulsion ointments containing amphoteric surfactants as emulsifiers. It has been shown that the rate of release can be evaluated by the distribution coefficient of the drug between the compartments as accurately as by the use of effective diffusion coefficients.

Studies on the release of drugs from O/W emulsion ointments using the mathematical interpretations. Part 3: Kinetic approach.

Kinetic models describing the drug release process from oil-in-water (O/W) emulsions through artificial membranes have been proposed. It has been shown that the kinetic approach appears to be useful in analysis of this problem.

Studies on the release of drugs from O/W emulsion ointments using the mathematical interpretations. Part 2: Influence of the ointment composition.

The empirical function Q = t/(A + Bt) has been applied to the quantitative description of the release process of salicylic acid from the emulsion ointment as influenced by its composition. The results as compared with those obtained by the use of Higuchi's "exponential" equation confirm the usefulness of the proposed equation, especially for thin ointment layers. It has been shown that there is a satisfactory correlation between the values of parameters 1/A, 1/B and thickness of the ointment layer and its composition. In this manner it is possible to predict the time course of the release process under other conditions.

Studies on the release of drugs from O/W-emulsion ointments using the mathematical interpretations. Part 1: Influence of the thickness of the ointment layer.

The hyperbolic function Q = t/(A + Bt) has been applied to the quantitative description of the release process from the emulsion ointment as influenced by the thickness of the layer. Results have been compared with the analogous ones obtained by the use of Higuchi's "exponential" equations. This comparison leads to the conclusion that the proposed empirical function is especially usefull for thin ointment layers.

Application of the modified one-compartment open model in pharmacokinetic investigations.

A simple method which uses a one-compartment open model to describe changes of concentration of a drug in blood plasma after rapid i.v. injection is described. Application of this method makes it possible to reduce the number of parameters which are necessary to describe experimental data.

Application of the simple mathematical function for the quantitative description of in vitro release of drug agents from the ointment bases.

An attempt of the quantitative description of the release process by the simple mathematical functions has been made. It was found that the hyperbolic function q = t/(A + Bt) is the best for this application. The values of the parameters 1/A and 1/B are proportional to the released amounts of drug, so they can be useful for the evaluation of the rate of the release process.