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Updated: Jan 14, 2026

Visualizing and Quantifying Pharmaceutical Compounds within Skin using Coherent Raman Scattering Imaging
Published on: November 24, 2021
Efficacy of Cryogenic Particle Delivery in Enhancing Skin Penetration and Absorption
Kyu-Ho Yi1,2, Jin-Hyun Kim3, Jong Keun Song4
1BK21 FOUR Project, Division in Anatomy and Developmental Biology, Department of Oral Biology, Human Identification Research Institute, Yonsei University College of Dentistry, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Korea. kyuho90@daum.net.
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 CO2 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.
Level Of Evidence V:
This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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