Showing papers by "Joke A. Bouwstra published in 2005"

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

Abstract: Summary Background 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. Objectives The aim of this study was to investigate the cutaneous side-effects of transdermal iontophoresis application in healthy human volunteers. Methods 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 µA 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. Results 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. Conclusions 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.

Structure of the Skin Barrier

Abstract: The skin is composed of several morphologically distinct layers. The skin is protected primarily by the stratum corneum (SC). The superficial region, which is only 10-20 mm thick, is the primary barrier to the percutaneous absorption of compounds, as well as to water loss. Underlying the SC is the viable epidermis (50-100 mm thick), which is responsible for generation of the SC. The dermis (1-2mm thick) is directly adjacent to the epidermis and provides the mechanical support for the skin. The viable epidermis is a stratified squamous epithelium consisting of basal, spinous, and granular cell layers. Each layer is defined by position, shape, morphology, and state of differentiation of keratinocytes. The epidermis is a dynamic, constantly self-renewing tissue, in which the loss of the cells from the surface of the SC (desquamation) is balanced by cell growth in the lower epidermis. Upon leaving the basal layer, keratinocytes begin to differentiate and during their apical migration through the stratum spinosum and stratum granulosum (SG), they undergo a number of changes in both structure and composition. The keratinocytes synthesize and express numerous different structural proteins and lipids during their maturation. The final steps in keratinocyte differentiation are associated with profound changes in their structure resulting in their transformation into corneocytes. The corneocytes are relatively flat, anucleated squamous cells packed mainly with keratin filaments, and surrounded by a cell envelope composed of cross-linked proteins, as well as a covalently bound lipid (CLE) envelope. This corneocyte lipid envelope most probably plays an important role in keeping the osmotically active material inside the corneocytes. Extracellular non-polar lipids surround the corneocytes, forming a hydrophobicmatrix. Furthermore, corneodesmosomes interconnect adjacent corneocytes and are important for the SC cohesion.