Evaluating Dermal Pharmacokinetics and Pharmacodymanic Effect of Soft Topical PDE4 Inhibitors: Open Flow Microperfusion and Skin Biopsies.

Purpose: To investigate the difference in clinical efficacy in AD patients between two topical PDE4 inhibitors using dermal open flow microperfusion and cAMP as a pharmacodynamic read-out in fresh human skin explants.

Methods: Clinical formulations were applied to intact or barrier disrupted human skin explants and both skin biopsy samples and dermal interstitial fluid was sampled for measuring drug concentration. Furthermore, cAMP levels were determined in the skin biopsies as a measure of target engagement.

Permeability and lipid organization of a novel psoriasis stratum corneum substitute.

Lipids in the uppermost layer of the skin, the stratum corneum (SC), play an important role in the skin barrier properties. The main lipid classes are ceramides, cholesterol and free fatty acids. In previous studies a stratum corneum substitute (SCS) was developed, solely prepared from the SC lipids.

Calcipotriol delivery into the skin with PEGylated liposomes.

The D-vitamin analogue calcipotriol is commonly used for topical treatment of psoriasis, but skin penetration is required for calcipotriol to reach its pharmacological target: the keratinocytes in the lower epidermis. Liposomes can enhance the delivery of drugs into the skin, but a major challenge for the development of dosage forms containing liposomes is to maintain the colloidal stability in the formulation. The purpose of this study was to investigate the effect of stabilising liposomes with the lipopolymer poly(ethylene glycol)-distearoylphosphoethanolamine (PEG-DSPE) on the physicochemical properties of the liposomes and the ability to deliver membrane-intercalated calcipotriol into the skin.

Risk assessment of topically applied products.

The human risk of harmful substances in semisolid topical dosage forms applied topically to normal skin and broken skin, respectively, was assessed. Bisphenol A diglycidyl ether (BADGE) and three derivatives of BADGE previously quantified in aqueous cream and the UV filters 3-BC and 4-MBC were used as model compounds. Tolerable daily intake (TDI) values have been established for BADGE and derivatives.