A physical method to enhance transdermal delivery of a tissue optical clearing agent: Combination of microneedling and sonophoresis

Abstract

Background and Objectives Various physical methods, such as microneedling, laser ablation, sonophoresis, and sandpaper, have been widely studied to enhance the transdermal delivery of tissue optical clearing (TOC) agents. A previous study demonstrated that the microneedling method could effectively enhance the permeability of a TOC agent through the skin barrier. Study Design/Materials and Methods In this study, we introduce a new physical combination method which utilizes both microneedling and sonophoresis to further enhance the transdermal delivery of a TOC agent, glycerol. Porcine skin samples were divided into a control group treated only with the microneedle roller and a test group treated with both the microneedle roller and sonophoresis. Glycerol was applied topically after microneedling. The optimal concentration and transdermal delivery efficacy of glycerol were quantitatively evaluated. Results A 70% glycerol solution was determined to be the optimal concentration for the combination method. The combination method resulted in approximately a 2.3-fold higher transdermal diffusion rate of glycerol when compared to the microneedling method alone. Conclusion The combination method and optimal glycerol concentration effectively enhanced transdermal delivery of glycerol by accelerating the diffusion rate through the skin barrier.

Optical clearing of biological tissues: prospects of application in medical diagnostics and phototherapy

“…However, at low concentrations OCAs do not provide sufficient optical clearing, while at high concentrations they can induce edema, chemical burn, partial necrosis and scarring [45,65,108]. To develop an efficient and safe way of breaking the integrity of the epidermis stratum corneum and accelerating the penetration of OCA into the dermis, various physical methods [56,118,[130][131][132][133][134][135][136][137][138][139][140], chemical enhancers of permeability [114,118,[141][142][143][144][145][146][147], and their combinations [118,148,149] have been proposed.…”

“…Beside the chemical agents, a number of physical methods of surmounting the skin barrier are proposed to enhance the diffusion, including low-and high-intensity irradiation [130,158], fractional lamp [131,133] and laser [132] microablation, mechanical microperforation [137,138], ultrasonic (US) irradiation [134,135,159], electrophoresis [160], needleless injection [161], mechanical removal of the surface layer by means of abrasive paper [136], epidermal stripping [162], and microdermabrasion [163].…”

“…Yoon et al [137] used this device, applied in cosmetology, to create transdermal microchannels in samples of porcine skin ex vivo with the aim of improving the glycerol penetration into the depth of the skin. The combination of multiple needle perforation with low-frequency ultrasonic effect allowed the increase of the diffusion rate of the 70% glycerol solution into the skin by 2.3 folds in comparison with using the multiple-needle roller solely [138].…”

Development of an Optical Tissue Clearing Laser Probe System

“…Although various OTC methods, such as mechanical (positive pressure and stretching), chemical (hyperosmotic chemical agent [HCA]), and thermal (temperature) methods, have been studied to minimize tissue turbidity by reducing light scattering in soft tissue [3][4][5][6], the clinical applications have not been sufficiently studied to date.…”

“…Tuchin clearly described the clinical diagnostic efficacy of chemical agents [23,24]. Recently, both Yoon et al and Kang et al reported that the combination of glycerol, compression, micro-needling, and sonophoresis decreased the diffusion time of glycerol and had a greater OTC effect than independent application [3][4][5][6]. Liu et al investigated various light irradiations to increase permeability of chemical agents and, therefore, enhance the efficacy of OTC [25].…”