Ex Vivo Evaluation of Skin Permeability Enhancement Using TargetCool in Human-Derived Skin Tissue Models

BACKGROUND: The stratum corneum presents a significant barrier to transdermal delivery. TargetCool is a cooling-assisted delivery device developed to enhance skin penetration, with potential synergistic effects when combined with microneedling systems such as the Turtle pin (0.5 mm) and MTS (1.5 mm). OBJECTIVE: This study aimed to evaluate the effect of TargetCool on the permeability of Acetyl Hexapeptide-8-FITC in an ex vivo human skin model, comparing its performance alone and in combination with microneedling devices. METHODS: Facial skin samples from Korean female donors aged 50 to 70 years were prepared into 2 × 2 cm sections and assigned to 6 groups: control (topical application only), Turtle pin 0.5 mm, MTS 1.5 mm, Turtle pin 0.5 mm plus TargetCool, MTS 1.5 mm plus TargetCool, and TargetCool alone. Samples were cultured for 24 hours in a Transwell system following treatment with Acetyl Hexapeptide-8-FITC, then processed for H&E and DAPI staining. Optical and fluorescence microscopy were used to assess tissue structure, fluorescence intensity, and penetration depth, with quantitative analysis performed using ImageJ. RESULTS: No structural damage was observed in any group. Compared with the control, fluorescence intensity increased by 504% with Turtle pin, 700% with MTS, 1272% with Turtle pin plus TargetCool, 1000% with MTS plus TargetCool, and 492% with TargetCool alone. Penetration depth increased by 19.01%, 33.10%, 36.88%, 47.75%, and 35.86%, respectively. CONCLUSION: TargetCool, particularly in combination with microneedling, substantially enhanced the skin penetration and depth of Acetyl Hexapeptide-8-FITC in ex vivo human skin without inducing structural damage. These findings support its potential clinical application in improving transdermal delivery for dermatologic and aesthetic treatments.