New lipophilic organic nitrates: candidates for chronic skin disease therapy.

Organic nitrates are widely used, but their chronic efficacy is blunted due to the development of tolerance. The properties of new tolerance free organic nitrates were studied. Their lipophilicity profile and passive diffusion across polydimethylsiloxane membrane and pig ear-skin, and their efficacy in tissue regeneration using HaCaT keratinocytes were evaluated. The permeation results show that these nitrates have a suitable profile for NO topical administration on the skin. Furthermore, the derivatives with higher NO release exerted a pro-healing effect on HaCaT cells. This new class of organic nitrates might be a promising strategy for the chronic treatment of skin pathologies.