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Background: In recent years, worldwide attention of researchers focused on the practical implementation of nanoscale materials in biomedical technology. It’s proved that intravenous injected gold nanoparticles are accumulated in tumor tissues. However, when gold nanoparticles injected intravenously negative effects in the internal organs of experimental animals are observed. 160 nm diameter particles affect the wall of blood vessels, resulting in vacuolar degeneration of endothelial cells. Particles with a diameter of 50 nm lead to more expressed changes in the internal organs. Injection of the particles diameter of 15 nm causes moderate degeneration of parenchymal cells of internal organs and circulatory disorders. Materials and Methods: In current research, for the first time using the methods of experimental pathology the permeability of intact and damaged skin for nanoscale gold particles in combination with organosulfur compounds—imethylsulfoxide and tiofansulfoxide were studied. We used 140 male outbred white rats with an average weight 150 - 200 grams. All the animals were divided into one control and three experimental groups. Results: Laser microperforation skin with ultrasound treatment can provide good skin permeability, but in contrast to use of agents with organosulfur compounds inflammatory reaction, the destruction of superficial and deep skin tissue structural elements are observed. The comparative efficacy of dimethylsulfoxide and tiofansulfoxide for transdermal permeability of gold nanoparticles was studied. It’s proved that in topical application solution of nanoparticles with organosulfur compounds negative effects of the accumulation of nanoparticles in the internal organs, disorders of organ and tissue microcirculation, development in the degenerative changes are not observed. We found that the depth of penetration of damaged skin (contact dermatitis) for the gold nanoparticles in combination with organosulfur compounds, and ultrasound exposure is substantially higher than the penetration of intact skin.