The findings provide further support for the use of CRS to monitor drug delivery into and across the skin. In addition, the results highlight the critical role of the vehicle and its disposition in skin for effective dermal delivery.

The techniques used in this study provide rapid noninvasive measures of the spatial distribution of corneocyte maturity and surface area as well as protease activity and protein content within different levels of the stratum corneum layers. The methods used will allow mechanistic insight into the effects of formulation excipients and active ingredients on epidermal turnover and skin barrier function.

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Several serine protease enzymes are known to be involved in both normal desquamation and the inflammatory processes of the skin. Alteration in the activity of these proteases should also affect corneocyte maturity and size as well as stratum corneum thickness. The aim of the present work was to characterise the baseline changes in corneocyte size, corneocyte maturity, selected protease activity (specifically, Kallikreins-5 and 7, tryptase), protein content and trans-epidermal water loss (TEWL) as a function of anatomic site. The anatomic sites investigated were: cheek, abdomen, wrist and mid-ventral forearm. TEWL values were highest for the cheek (p < 0.05). The TEWL values were also significantly higher (p < 0.05) for cheek and wrist compared with other sites. Protein content was significantly lower for wrist (p < 0.05) compared with other sites. Corneocyte maturity and surface area were significantly (p < 0.05) lower for cheek and wrist compared with other sites. An excellent correlation (r (2) = 0.99) was obtained for maturity and surface area measurements. Kallikrein-5 and tryptase activity were significantly higher for the cheek compared with other sites but Kallikrein-7 values were uniform across sites. The findings have significant implications for skin permeability to drugs and other substances such as environmental toxins depending on the anatomic site of delivery or exposure.

SummaryBackground Aqueous Cream BP is frequently prescribed for patients with eczema and is known to induce sensitivity in certain patients and also to decrease the thickness of the stratum corneum (SC). We have previously reported methodology to quantify corneocyte maturity and size, protease activity and protein content within different levels of the SC. Objectives The aim of the present study was to investigate changes in corneocyte size, corneocyte maturity, selected protease activities, protein content and transepidermal water loss (TEWL) in normal skin after a 28-day application of Aqueous Cream BP. Methods The left and right mid volar forearms of six healthy female volunteers were selected as the study sites. Aqueous Cream BP was applied twice daily to treated sites for 28 days. At the end of this period, the site was tape-stripped and corneocyte maturity, corneocyte size and protease activity of the desquamatory kallikrein proteases, KLK5 and KLK7, and the inflammatory proteases tryptase and plasmin were measured. Protein content and TEWL measurements were also recorded. Results Corneocyte maturity and size decreased with increasing number of tape strips, and were significantly lower in treated sites compared with untreated sites. Protease activity and TEWL values were higher (P < 0AE05) for the treated sites compared with untreated sites. The amount of protein removed from deeper layers of treated sites was significantly lower than from untreated sites. Conclusions We report rapid minimally invasive measures of the effects of Aqueous Cream BP at the cellular and molecular level of the skin. Treatment with this formulation is associated with increased desquamatory and inflammatory protease activity. Changes in corneocyte maturity and size are also indicative of accelerated skin turnover induced by chronic application of this emollient. These findings question firmly the routine prescription of this preparation as a moisturizer in patients with atopic dermatitis.