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Ultrasonic Transdermal Delivery System with Acid-Base Neutralization-Generated CO2 Microbubble Cavitation
Yi-Ju Ho1, Hui-Ching Hsu1, Shih-Tsung Kang1,2
1Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 30013, Taiwan.
ACS Applied Bio Materials
|January 13, 2022
Summary
This study introduces a simple, self-operating ultrasonic system using carbon dioxide microbubbles (CO2-MBs) to enhance transdermal drug delivery. This method significantly improves drug penetration through the skin for potential in-home healthcare applications.
Area of Science:
- Biomedical Engineering
- Materials Science
- Pharmacology
Background:
- Transdermal drug delivery offers a noninvasive route for medication administration, crucial for in-home healthcare.
- The skin's stratum corneum presents a significant barrier to drug penetration.
- Ultrasound (US)-stimulated microbubble (MB) cavitation is a promising method to enhance skin permeability.
Purpose of the Study:
- To develop a simple and self-operating ultrasonic transdermal delivery system.
- To create shell-free carbon dioxide microbubbles (CO2-MBs) for enhanced drug penetration.
- To evaluate the efficacy of CO2-MB cavitation in improving transdermal drug delivery.
Main Methods:
- Shell-free CO2-MBs were generated using citric acid and NaHCO3 via acid-base neutralization.
- US sonication parameters: 3.1 MHz, 0.5 W/cm², 50% duty cycle for 1 minute.
- Drug penetration was assessed using Evans blue and FITC-conjugated hyaluronic acid in rat skin models.
Main Results:
- CO2-MB generation rate was 36.3 ± 10 MBs/s with a mean size of 110 ± 14 μm.
- Transdermal penetration of Evans blue and FITC-hyaluronic acid increased by 2.4 ± 0.3 and 2.1 ± 0.1 fold, respectively.
- Evans blue penetrated to a depth of 27.1 ± 5.1 μm, reaching the epidermal layer.
Conclusions:
- A simple, self-operating ultrasonic transdermal delivery system utilizing CO2-MB cavitation was successfully developed.
- This system effectively enhances transdermal drug penetration, showing potential for transcutaneous immunization.
- The findings support the application of this technology for improved in-home healthcare drug delivery.

