Topical delivery of climbazole to mammalian skin

Dandruff is a common condition, affecting up to half the global population of immunocompetent adults at some time during their lives and it has been highly correlated with the over-expression of the fungus Malassezia spp. Climbazole (CBZ) is used as an antifungal and preservative agent in many marketed formulations for the treatment of dandruff. While the efficacy of CBZ in vitro and in vivo has previously been reported, limited information has been published about the uptake and deposition of CBZ in the skin. Hence, our aim was to investigate the skin permeation of CBZ as well as the influence of various solvents on CBZ skin delivery. Four solvents were selected for the permeability studies of CBZ, namely propylene glycol (PG), octyl salicylate (OSal), Transcutol® P (TC) and polyethylene glycol 200 (PEG). The criteria for selection were based on their wide use as excipients in commercial formulations, their potential to act as skin penetration enhancers and their favourable safety profiles. 1% (w/v) solutions of CBZ were applied under infinite and finite dose conditions using Franz type diffusion cells to human and porcine skin. In line with the topical use of CBZ as an antidandruff agent, comparatively low amounts of CBZ penetrated across the skin barrier ( 7-fold) compared with human skin (p<0.05). Nevertheless, no statistical differences were observed in the amounts that permeated across the different membranes. These preliminary results confirm the potential of simple formulations of CBZ to target the outer layers of the epidermis. The PG and OSal formulations appear to be promising vehicles for CBZ in terms of overall skin extraction and penetration. Future work will expand the range of vehicles studied and explore the reasons underlying the retention of CBZ in the outer layers of the skin

Brillouin microscopy for the evaluation of hair micromechanics and effect of bleaching

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this recordBrillouin microscopy is a new form of optical elastography and an emerging technique in mechanobiology and biomedical physics. It was applied here to map the viscoelastic properties of human hair and to determine the effect of bleaching on hair properties. For hair samples, longitudinal measurements (i.e. along the fibre axis) revealed peaks at 18.7 GHz and 20.7 GHz at the location of the cuticle and cortex, respectively. For hair treated with a bleaching agent, the frequency shifts for the cuticle and cortex were 19.7 GHz and 21.0 GHz, respectively, suggesting that bleaching increases the cuticle modulus and - to a minor extent - the cortex modulus. These results demonstrate the capability of Brillouin spectroscopy to address questions on micromechanical properties of hair and to validate the effect of applied treatments.Engineering and Physical Sciences Research Council (EPSRC)UnileverCancer Research UKEuropean Unio

Modeling transdermal permeation. Part 2. Predicting the dermatopharmacokinetics of percutaneous solute

The prediction of percutaneous absorption and bioavailability in vivo, using the recently reported "bricks-and-mortar" model is discussed. Two sets of in vivo data have been simulated: the tape-striping data of 4-cyanophenol and Raman spectrometry data of transretinol. The predicted transdermal permeation using theoretically derived properties agreed well with the experimental data. The prediction shows that about 2/3 of the 4-cynophenol in the SC partitioned into the corneocytes, indicating diffusion of moderately hydrophobic solutes across the corneocytes is also important. Only for highly hydrophobic solute like transretinol, diffusion across the corneocytes is negligibly small. The study demonstrates that with the mechanism-based computer model, many dermatopharmacokinetic parameters can be derived, providing much insight into how vehicle formulation and topical administration affects the absorption and distribution of solute in the SC, as well as its bioavailability in epidermis/dermis. © 2010 American Institute of Chemical Engineers (AIChE)