Qualitative and quantitative comparison of heat separated epidermis and dermatomed skin in percutaneous absorption studies

Transepidermal water loss (TEWL), mainly regulated by the stratum corneum, was quantitatively correlated to percutaneous absorption of compounds in human and suggested for the ex vivo assessment of skin integrity. The present study investigated qualitatively and quantitatively the relevance of 100-mu m heat separated epidermis (HSE) in percutaneous absorption studies as compared to 500-mu m dermatomed skin by dual complementary approaches. Percutaneous absorption of caffeine delivered from aqueous solution through dermatomed skin or HSE specimens (n = 9) was measured using vertical static diffusion cells coupled with an unventilated evaporimeter enabling the assessment of TEWL and skin integrity for 21 h. Permeation of caffeine exhibited different finite dose-like profiles ranged according to the thickness of skin specimens (cumulative dose absorbed up to 21 h: 11.5 +/- 11.5 mu g/cm(2) and 29.4 +/- 36.2 mu g/cm(2) through dermatomed skin and HSE, respectively). Normalized TEWL and caffeine fluxes were similar through dermatomed skin and HSE suggesting that the intrinsic permeability properties of both models were undifferentiated over time. Interestingly, a significant relationship was shown between TEWL and caffeine fluxes, suggesting the usefulness of TEWL measurement as an element in the estimation of percutaneous drug absorption. In conclusion, the present showed that percutaneous absorption through HSE was qualitatively and quantitatively similar to dermatomed skin when TEWL as endogenous standard and skin thickness were considered in permeability data comparisons

Internalisation of hybrid titanium dioxide/para-amino benzoic acid nanoparticles in human dendritic cells did not induce toxicity and changes in their functions

Migdal, Camille Rahal, Raed Rubod, Alain Callejon, Sylvie Colomb, Evelyne Atrux-Tallau, Nicolas Haftek, Marek Vincent, Claude Serres, Mireille Daniele, StephaneInternational audienceNanoparticles (NPs) have been reported to penetrate into human skin through lesional skin or follicular structures. Therefore, their ability to interact with dendritic cell (DC) was investigated using DCs generated from monocytes (mono-DCs). Hybrid titanium dioxide/para-amino benzoic acid (TiO2/PABA) NPs did not induce any cell toxicity. NPs were internalised into DCs through macropinocytosis and not by a receptor-mediated mechanism. Confocal microscopy showed that NPs were not detected in the nucleus. These data are confirmed by electronic microscopy which demonstrated that hybrid NPs were rapidly in contact with cellular membrane and localised into cytoplasmic vesicles without colocalisation with clathrin-coated vesicles. Hybrid NPs did not induce CD86 or HLA-DR overexpression or cytokine secretion (IL-8 and TNF-alpha) indicating no DC activation. Internalisation of hybrid NPs did not modify DC response towards sensitisers such as nickel and thimerosal or LPS used as positive controls. Moreover, hybrid NPs did not induce any oxidative stress implicated in DC activation process. After mono-DC irradiation by ultraviolet A (UVA), hybrid NP-treated cells did not produce UVA-induced reactive oxygen species (ROS) and exhibited a better cell viability compared with UVA-irradiated control cells, suggesting a protecting effect of hybrid TiO2/PABA NPs against UVA-induced ROS. (C) 2010 Elsevier Ireland Ltd. All rights reserved

Design and characterization of diclofenac diethylamine transdermal patch using silicone and acrylic adhesives combination

<p>Abstract</p> <p>Background and purpose of the study</p> <p>The objective of the study was to develop and characterize Diclofenac Diethylamine (DDEA) transdermal patch using Silicone and acrylic adhesives combination.</p> <p>Methods</p> <p>Modified solvent evaporation method was employed for casting of film over Fluoropolymer coated polyester release liner. Initial studies included solubilization of drug in the polymers using solubilizers. The formulations with combination of adhesives were attempted to combine the desirable features of both the adhesives. The effect of the permeation enhancers on the drug permeation were studied using pig ear skin. All the optimized patches were subjected to adhesion, dissolution and stability studies. A 7-day skin irritancy test on albino rabbits and an in vivo anti-inflammatory study on wistar rats by carrageenan induced paw edema method were also performed.</p> <p>Results</p> <p>The results indicated the high percent drug permeation (% CDP-23.582) and low solubility nature (1%) of Silicone adhesive and high solubility (20%) and low% CDP (10.72%) of acrylic adhesive. The combination of adhesives showed desirable characteristics for DDEA permeation with adequate % CDP and sufficient solubility. Release profiles were found to be dependent on proportion of polymer and type of permeation enhancer. The anti-inflammatory study revealed the sustaining effect and high percentage inhibition of edema of C4/OLA (99.68%). The acute skin irritancy studies advocated the non-irritant nature of the adhesives used.</p> <p>Conclusion</p> <p>It was concluded that an ideal of combination of adhesives would serve as the best choice, for fabrication of DDEA patches, for sustained effect of DDEA with better enhancement in permeation characteristics and robustness.</p