Tape stripping and sodium dodecyl sulfate treatment increase the molecular weight cutoff of polyethylene glycol penetration across murine skin

Abstract

Prior studies in hairless mice have demonstrated that acute barrier disruption by acetone treatment increases the molecular weight (MW) cutoff of polyethylene glycol (PEG) penetration through the skin. The objective of the present study was to further investigate the dependence of permeability on MW with different forms of barrier disruption. A series of PEGs ranging in MW from near 300 to over 1000 Da were used to study the effects of tape stripping and sodium dodecyl sulfate (SDS) treatment on the MW permeability profiles of mouse skin in vitro. The 12-h percutaneous penetration of all the PEG 300, 600, and 1000 oligomers generally increased as a function of transepidermal water loss (TEWL) of the skin, either tape-stripped or SDS-treated. In addition, the total penetration of PEG oligomers across control skin, and skin tape-stripped and SDS-treated to different degrees of barrier disruption progressively decreased with increasing MW. There were no significant differences in the percutaneous penetration of the PEG oligomers between skin tape-stripped and SDS-treated to the same degree of barrier disruption. The penetration enhancement relative to control skin was more prominent with larger molecules. The MW cutoff for skin penetration increased with the degree of barrier disruption irrespective of the treatment applied, and was 986 Da (tape stripping) and 766 Da (SDS treatment) at TEWL levels in the range 10-20 g/m(2) per h in comparison with 414 Da for control skin. In accordance with previous findings in acetone-treated mouse skin, the results strongly suggest that, irrespective of the form of barrier disruption applied, not only higher amounts but also more varieties of chemicals (larger molecules) may penetrate skin with a compromised barrier than normal skin.

A GRHL3-regulated repair pathway suppresses immune-mediated epidermal hyperplasia

“…When Grhl3 cKO wax-stripped mice were allowed to recover for 2 or 3 full weeks, they continued to show significant hyperplasia of their epidermis, with a strong presence of CD45 + immune cells within the dermis and along the epidermal-dermal junction (Supplemental Figure 3). Similar results to stripping were found after topical skin application of SDS, which disrupts the epidermal barrier by removing the protective epidermal lipids (27); after 2 days of recovery, Grhl3 cKO mice showed more severe damage, hyperplasia, and increased TEWL (Supplemental Figure 4, A and B). Together, these observations demonstrated that Grhl3 is critical for the suppression of epidermal hyperproliferation and reconstruction of the epidermal barrier during repair of a barrierdisrupting injury in adult skin.…”

Evaluation of in Vitro Release of Diclofenac Sodium Formulated Gels through Diffusion Cell

“…It is evident from Figure 2 that the percent release further increased, reaching about 83% at the end of 6 hours (84.61 % at 24 hours) in comparison to about 74% from micro emulsion gel. Enhanced release with SLS-soaked membrane from Hydrogel is in agreement with the higher diffusion of drug particles occurring as a result of pretreatment with anionic emulsifiers 12,13 .…”

Delivery of drugs applied topically to the skin

“…As the SC thickness is reduced, there is increased water loss across the membrane, indicated by increased TEWL [115]. There is also evidence that reducing the SC thickness by tape stripping effectively expands the possible size range of penetrants, as Tsai et al demonstrated that the MW cutoff for skin penetration of polyethylene glycol oligomers increased in parallel with barrier disruption, shown by increasing TEWL as the skin was tape stripped [116]. While tape stripping is a useful investigatory tool for examining mechanisms of skin penetration and can also be used to sample penetrants retained in the SC in order to obtain depth or kinetic profiles, it has little practical or commercial value as a drug delivery technique.…”