In particular, intermediate filaments constituting up to 70% of t

In particular, intermediate filaments constituting up to 70% of the total dry weight mass of the stratum corneum are coassembles of basic subunits (i.e. type I keratin) and acidic subunits (i.e. type II keratin) having an average molecular weight ranging from 50 to 70▒kDa [9]. Moreover, keratins are classified on the basis of the sulphur PD-1/PD-L1 phosphorylation content which reflects the cross-linking extent and, therefore, its resistance. Due to the low sulphur content, in stratum corneum “soft-keratin” is present. A further classification is based on x-ray diffraction patterns obtained from different keratin proteins. Alpha-helixes

appear to be the basis of fibrillar elements in keratins from mammalians [8]. The continuous lipid bilayer is made of various classes of lipids, namely cholesterol, cholesterol esters, free fatty acids, triglycerides and ceramides (CERs), which are arranged in two coexisting lamellar phases; a long periodicity phase with a repeat distance of about 13▒nm and a short periodicity phase with a repeat distance of about 6▒nm [10,11]. In particular, CERs have drawn much attention since changes in the CER composition play a role in an impaired skin barrier [12,13]. The various CERs consist of a long-chain sphingoid base linked via an amide bond to a fatty acid and, until now, twelve human CER subclasses have been identified

differing in polar head group and chain length [14]. Because of the crucial role of the lipids in the skin barrier function, selleck kinase inhibitor an in vitro model consisting of a porous substrate covered with a layer of synthetic lipids was proposed as a tool to predict solute permeation through human skin [ 15, 16]. A basic lipid model membrane composed of only four constituents 5-Fluoracil datasheet was also prepared on porous substrates to study the impact of each CER species on the diffusion and penetration of drugs [ 17]. To match the permeability of the stratum corneum, synthetic certramides, which are analogues of the ceramides, were selected to develop a skin Parallel Artificial Membrane Permeability Assay (PAMPA) model [ 18]. The present work aimed to develop a membrane made of a limited number of

CERs and keratin which could mimic the barrier property of the human stratum corneum in in vitro percutaneous absorption studies. The membrane composition was optimized reducing the number of components in order to simplify its preparation and favour the reproducibility. The membrane performances were tested using three model molecules chosen on the basis of their different diffusion and solubility properties: (RS)-ibuprofen [ 19], (RS)-propranolol [ 20] and testosterone [ 1]. The drug permeation amounts were compared to those obtained in a set of experiments carried out using human epidermis as membrane [ 1, 2]. (RS)-Ibuprofen (IB) and testosterone (TS) were obtained from A.C.E.F. (Italy) and Sigma-Aldrich (Italy), respectively. (RS)-Propanolol (PR) was kindly gifted by S.I.M.S. (Italy).

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