Efficacy of Cryogenic Particle Delivery in Enhancing Skin Penetration and Absorption

Abstract

Background Cryogenic particle delivery is a novel cryotherapy-based transdermal delivery system that converts liquid drugs into micro-ice-crystallised needles, which are propelled into the skin using a cryogenic CO(2 )jet. This study evaluates its efficacy in enhancing skin penetration and absorption, alone and in combination with the Microneedle Therapy System (MTS). Objective To assess fluorescence intensity, penetration depth, and structural integrity in ex vivo human skin tissues treated with cryogenic particle delivery, MTS, or a combination of both. Methods Ex vivo human skin tissues were divided into four groups: untreated (Control), MTS alone (Control 1), MTS combined with cryogenic particle delivery (Control 2), and Picolitre ice particle delivery alone (Test Group). Fluorescence-labelled hyaluronic acid (HA-FITC) was applied, and fluorescence intensity and penetration depth were evaluated using confocal microscopy. Structural integrity was assessed through haematoxylin and eosin (H&E) staining. Statistical analysis was performed using paired t tests (p < 0.05). Results Fluorescence intensity increased significantly in all treated groups compared to the untreated control: by 279.06 (MTS alone), 492.81 (MTS + cryogenic particle delivery), and 251.88% (cryogenic particle delivery alone) (p < 0.05). Penetration depth also increased significantly: by 52.00 (MTS alone), 60.06 (MTS + cryogenic particle delivery), and 36.99% (Cryogenic particle delivery alone). H&E staining confirmed no structural damage in any group. Conclusion Cryogenic particle delivery significantly enhances skin penetration and absorption, particularly when combined with MTS, demonstrating a synergistic effect. Its ability to deliver compounds safely and effectively highlights its potential as a transformative tool for therapeutic and cosmetic transdermal applications. Future in vivo studies are warranted to validate these findings and optimise its clinical applications.