Optical clearing as method to increase the depth of nanoparticles detection in the skin with OCT-visualization

Background and Objectives: Nanoparticles of titanium dioxide are now widely used both for the creation of sunscreen filters, and as carriers of drugs. One of the ways of transepidermal delivery of these nanoparticles to the dermis of the skin is their penetration into the hair follicles. However, optical control of the filling of follicles with nanoparticles is rather difficult due to strong light scattering in the skin. Thus, the aim of the work is to investigate the possibility of increasing the optical depth of detection of nanoparticles in the hair follicle by means of optical coherence tomography in optical skin clearing. Methods and Materials: An optical coherent tomograph was used to visualize titanium nanoparticles with a diameter of $\sim$25 nm, localized in the hair follicles of laboratory rats ex vivo and in vivo. For the introduction of nanoparticles into the follicles, ultrasonophoresis was used with a frequency of 1 MHz, a power of 1 W, and an irradiation time of 1 to 8 min. To increase the optical depth of detection of particles, immersion agents were additionally applied on the surface of the skin: PEG-400 or a mixture of PEG-400 and DMSO. Results: It was shown that when using a mixture of PEG-400 and DMSO, the depth of detection increased by an average of 2.8 times, while using only PEG-400, the optical depth of detection of particles increased by less than 20%. Conclusion: Thus, the use of optical clearing agents made it possible to increase the optical depth of detection of nanoparticles in the hair follicles, with the greatest efficiency demonstrated by a mixture of PEG-400 and DMSO.