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A. Walicka and B. Iwanowska-Chomiak

Abstract

The stratum corneum (SC) forms the outermost layer of the human skin and is essentially a multilamellar lipid milieu punctuated by protein-filled corneocytes that augment membrane integrity and significantly increase membrane tortuosity. The lipophilic character of the SC, coupled with its intrinsic tortuosity, ensure that it almost always provides the principal barrier to the entry of drug molecules into the organism. Drugs can be administered either as suspensions or as solutions and the formulation can range in complexity from a gel or and ointment to a multilayer transdermal path. In this paper, we discuss theoretical principles used to describe transdermal release and we show that relatively simple membrane transport models based on the appropriate solution to the Fick’s second law of diffusion can be used to explain drug release kinetics into such a complex biological membrane as the human skin. To apply the Fick’s law we introduced into our considerations a brick-and-mortar model with two factors of tortuosity. Assuming that the mortar thickness is variable we also introduced the hindrance factor allowing us to model this variability. Having the modified Fick’s equation we presented its general solution and two special cases of this solution frequently applicable in permeation experiments. It seems that the solutions presented herein better approximate the real conditions of drug delivery then these well known.

Open access

A. Walicka and B. Iwanowska-Chomiak

Abstract

Skin, separating the vital organs of a human body, is a desirable route for drug delivery. However, the intact skin is normally permeable only for drug molecules with a low molecular weight. The stratum corneum (SC), being the outermost layer of the skin and the epidermis being the second – more permeable – layer of the skin, play an essential function in transdermal drug delivery. Physical and chemical methods of skin poration are used to enhance transdermal drug delivery. Each poration leads to an irregular system of pores which are connected with a system of micro-capillaries passing through the epidermis. Both the systems by their irregularity form a fractal porous matrix. Drugs administrated by this matrix can be either suspensions and solutions or creams and gels, therefore they have to be modelled as non-Newtonian fluids.

To analyse the fluid flow through the porous matrix the model of the epidermis is assumed as gobbet-andmortar with the tortuous mortar of variable thickness and after transition from the mortar to the tube one considered classical and fractal capillary flows of selected non-Newtonian fluids.

Fractal expressions for the flow rate, velocity and permeability of fluids flow in a porous matrix are derived based on the fractal properties of the epidermis and capillary model. Each parameter in the proposed expressions does not contain any empirical constant and has a clear physical meaning and the proposed fractal models relate the flow properties of considered fluids with the structural parameters of the epidermis as a porous medium. The presented analytical expressions will help understand some of the physical principles of transdermal drug delivery.

Open access

Ada Stelmakienė, Kristina Ramanauskienė and Vitalis Briedis

Abstract

The aim of this study was to evaluate the release of rosmarinic acid (RA) from the experimental topical formulations with the Melissa officinalis L. extract and to evaluate its penetration through undamaged human skin ex vivo. The results of the in vitro release study showed that higher amounts of RA were released from the emulsion vehicle when lemon balm extract was added in its dry form. An inverse correlation was detected between the released amount of RA and the consistency index of the formulation. Different penetration of RA into the skin may be influenced by the characteristics of the vehicle as well as by the form of the extract. The results of penetration assessment showed that the intensity of RA penetration was influenced by its lipophilic properties: RA was accumulating in the epidermis, while the dermis served as a barrier, impeding its deeper penetration.

Open access

Oliver Pabst

Abstract

It has been demonstrated before that human skin can be modeled as a memristor (memory resistor). Here we realize a memristor bridge by applying two voltages of opposite signs at two different skin sites. By this setup it is possible to use human skin as a frequency doubler and half-wave rectifier which is an application of the non-linear electrical properties of human skin. The corresponding electrical measurements are non-linear since these are affected by the applied stimulus itself.

Open access

David Basketter, Dagmar Jírova and Helena Kandárová

Abstract

Regulatory classification of skin irritation has historically been based on rabbit data, however current toxicology processes are transitioning to in vitro alternatives. The in vitro assays have to provide sufficient level of sensitivity as well as specificity to be accepted as replacement methods for the existing in vivo assays. This is usually achieved by comparing the in vitro results to classifications obtained in animals. Significant drawback of this approach is that neither in vivo nor in vitro methods are calibrated against human hazard data and results obtained in these assays may not correspond to situation in human.

The main objective of this review was to establish an extended database of substances classified according to their human hazard to serve for further development of alternative methods relevant to human health as well as resource for improved regulatory classification. The literature has been reviewed to assemble all the available information on the testing of substances in the human 4 h human patch test, which is the only standardized protocol in humans matching the exposure conditions of the regulatory accepted in vivo rabbit skin irritation test.

A total of 81 substances tested according to the defined 4 h human patch test protocol were found and collated into a dataset together with their existing in vivo classifications published in the literature. While about 50% of the substances in the database are classified as irritating based on the rabbit skin test, on using the 4 h HPT test, less than 20% were identified as acutely irritant to human skin. Based on the presented data, it can be concluded that the rabbit skin irritation test largely over-predicts human responses for the evaluated chemicals. Correct classification of the acute skin irritation hazard will only be possible if newly developed in vitro toxicology methods will be calibrated to produce results relevant to man.

Open access

Slobodan Stojanović, Nada Vučković and Marina Jovanović

Abstract

Ulerythema ophryogenes and keratosis follicularis spinulosa decalvans are rare folliculocentric keratotic disorders, from the group of follicular genokeratoses, characterized by keratosis pilaris atrophicans: follicular keratotic papules, sometimes with surrounding erythema, which eventually result in fibrosis, atrophy, progressive scarring and permanent hair loss. Ulerythema ophryogenes begins at birth or soon thereafter; it involves the lateral eyebrows, spreads medially and eventually affects the entire eyebrows, cheeks, and less frequently, forehead and asjecebt scalp. Involvement of the scalp has apparently not been reported in cases in which the eyebrows were predominantly involved. In addition to sporadic cases, ulerythema ophryogenes has been reported among relatives. Keratosis follicularis spinulosa decalvans is also a genetically heterogeneous syndrome which begins in infancy or childhood by involving hair bearing skin, especially the scalp; rarely it is confined to the face involving only eyebrows and eyelashes, but affects predominantly the scalp, leading to severe progressive cicatricial alopecia. Both conditions tend to progress until puberty.

The authors present a case of an otherwise healthy 19-year-old male patient, with absence of lateral eyebrows since childhood, which spread symmetrically and medially, until puberty affecting the entire eyebrows, whereas the eyelashes were completely spared. On examination, skin findings on the face, trunk and extremities pointed to ulerythema ophryogenes: apart from hair loss, the lateral eyebrows were highly erythematous; a great number of disseminated follicular, slightly keratotic papules (keratosis pilaris) pin- or match-head sized, were seen on the trunk, extensor surface of the arms and legs, as well as the buttock, and on palpation the skin felt like a “nutmeg grater”. However, follicle-based erythematous papules (focal patchy alopecia) were found not only along the eyebrows but also partly in the parietal capillitium forming focal patchy alopecia, which is a finding characteristic for keratosis follicularis spinulosa decalvans; the histopathological analysis of the biopsy specimens taken from the parietal capillitium has confirmed the clinical diagnosis.

Cytogenetic analysis showed no karyotypic abnormalities. Family history showed that the patient’s mother and maternal grandfather also suffered from hair loss especially of the lateral eyebrows.

This paper presents an overlap between two rare follicular genokeratoses in a young male with a positive family history, who presented with ulerythema ophryogenes involving not only the eyebrows, but also the scalp, in the form of parietal, focal cicatricial patchy alopecia.